The Experts below are selected from a list of 2520 Experts worldwide ranked by ideXlab platform
Patrizia Stoitzner - One of the best experts on this subject based on the ideXlab platform.
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Murine Langerin+ dermal dendritic cells prime CD8+ T cells while Langerhans cells induce cross‐tolerance
Embo Molecular Medicine, 2020Co-Authors: Vincent Flacher, Ralph M Steinman, Christoph H Tripp, Patrizia Stoitzner, David G Mairhofer, Juliana Idoyaga, Nikolaus RomaniAbstract:Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8+ T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin+ dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)-coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin+ dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8+ T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8+ T cells. Langerin/OVA combined with imiquimod could not prime CD8+ T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin+ dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8+ T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation programs.
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Murine Langerin + dermal dendritic cells prime CD8 + T cells while Langerhans cells induce
2020Co-Authors: Vincent Flacher, Ralph M Steinman, Christoph H Tripp, Patrizia Stoitzner, David G Mairhofer, Juliana Idoyaga, Nikolaus RomaniAbstract:Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8 + T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin + dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin + dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8 + T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8 + T cells. Langerin/OVA combined with imiquimod could not prime CD8 + T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin + dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8 + T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation
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murine Langerin dermal dendritic cells prime cd8 t cells while langerhans cells induce cross tolerance
Embo Molecular Medicine, 2014Co-Authors: Vincent Flacher, Ralph M Steinman, Christoph H Tripp, Patrizia Stoitzner, David G Mairhofer, Juliana Idoyaga, Nikolaus RomaniAbstract:Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8+ T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin+ dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)-coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin+ dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8+ T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8+ T cells. Langerin/OVA combined with imiquimod could not prime CD8+ T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin+ dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8+ T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation programs.
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anatomical distribution analysis reveals lack of Langerin dermal dendritic cells in footpads and tail of c57bl 6 mice
Experimental Dermatology, 2014Co-Authors: Benjamin Voisin, Patrizia Stoitzner, David G Mairhofer, Suzie Chen, Christopher G Mueller, Vincent FlacherAbstract:Epidermal Langerhans cells (LCs) and dermal dendritic cells (dDCs) capture cutaneous antigens and present them to T-cells in lymph nodes (LNs). The function of LCs and Langerin+ dDCs was extensively studied in the mouse, but their anatomical repartition is unknown. Here, we found LCs in back skin, footpads and tail skin of C57BL/6, BALB/c, 129/Sv and CBA/J mice. Langerin+ dDCs were readily observed in back skin of all strains, but only in footpads and tail of BALB/c and CBA/J mice. Similarly, while LCs were equally present in all LNs and strains, Langerin+ dDCs were found in popliteal LNs (draining footpads) only in BALB/c and CBA/J mice. The sciatic LNs, which we identified as the major tail-draining lymphoid organ, were devoid of Langerin+ dDCs in all strains. Thus, functionally different DCs reside in different skin areas, with variations among mouse strains, implying a potential impact on the cutaneous immune reaction.
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Anatomical distribution analysis reveals lack of Langerin+ dermal dendritic cells in footpads and tail of C57BL/6 mice.
Experimental Dermatology, 2014Co-Authors: Benjamin Voisin, Patrizia Stoitzner, David G Mairhofer, Suzie Chen, Christopher G Mueller, Vincent FlacherAbstract:Epidermal Langerhans cells (LCs) and dermal dendritic cells (dDCs) capture cutaneous antigens and present them to T-cells in lymph nodes (LNs). The function of LCs and Langerin+ dDCs was extensively studied in the mouse, but their anatomical repartition is unknown. Here, we found LCs in back skin, footpads and tail skin of C57BL/6, BALB/c, 129/Sv and CBA/J mice. Langerin+ dDCs were readily observed in back skin of all strains, but only in footpads and tail of BALB/c and CBA/J mice. Similarly, while LCs were equally present in all LNs and strains, Langerin+ dDCs were found in popliteal LNs (draining footpads) only in BALB/c and CBA/J mice. The sciatic LNs, which we identified as the major tail-draining lymphoid organ, were devoid of Langerin+ dDCs in all strains. Thus, functionally different DCs reside in different skin areas, with variations among mouse strains, implying a potential impact on the cutaneous immune reaction.
Nikolaus Romani - One of the best experts on this subject based on the ideXlab platform.
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Murine Langerin+ dermal dendritic cells prime CD8+ T cells while Langerhans cells induce cross‐tolerance
Embo Molecular Medicine, 2020Co-Authors: Vincent Flacher, Ralph M Steinman, Christoph H Tripp, Patrizia Stoitzner, David G Mairhofer, Juliana Idoyaga, Nikolaus RomaniAbstract:Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8+ T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin+ dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)-coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin+ dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8+ T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8+ T cells. Langerin/OVA combined with imiquimod could not prime CD8+ T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin+ dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8+ T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation programs.
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Murine Langerin + dermal dendritic cells prime CD8 + T cells while Langerhans cells induce
2020Co-Authors: Vincent Flacher, Ralph M Steinman, Christoph H Tripp, Patrizia Stoitzner, David G Mairhofer, Juliana Idoyaga, Nikolaus RomaniAbstract:Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8 + T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin + dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin + dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8 + T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8 + T cells. Langerin/OVA combined with imiquimod could not prime CD8 + T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin + dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8 + T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation
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murine Langerin dermal dendritic cells prime cd8 t cells while langerhans cells induce cross tolerance
Embo Molecular Medicine, 2014Co-Authors: Vincent Flacher, Ralph M Steinman, Christoph H Tripp, Patrizia Stoitzner, David G Mairhofer, Juliana Idoyaga, Nikolaus RomaniAbstract:Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8+ T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin+ dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)-coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin+ dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8+ T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8+ T cells. Langerin/OVA combined with imiquimod could not prime CD8+ T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin+ dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8+ T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation programs.
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murine Langerin dermal dendritic cells prime cd8 t cells while langerhans cells induce
2014Co-Authors: Vincent Flacher, Ralph M Steinman, Christoph H Tripp, Patrizia Stoitzner, David G Mairhofer, Juliana Idoyaga, Nikolaus RomaniAbstract:Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8 + T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin + dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin + dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8 + T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8 + T cells. Langerin/OVA combined with imiquimod could not prime CD8 + T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin + dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8 + T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation
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skin Langerin dendritic cells transport intradermally injected anti dec 205 antibodies but are not essential for subsequent cytotoxic cd8 t cell responses
Journal of Immunology, 2012Co-Authors: Vincent Flacher, Adrien Kissenpfennig, Bernard Malissen, Christoph H Tripp, Patrizia Stoitzner, Juliana Idoyaga, Bernhard Haid, Nikolaus RomaniAbstract:Incorporation of Ags by dendritic cells (DCs) increases when Ags are targeted to endocytic receptors by mAbs. We have previously demonstrated in the mouse that mAbs against C-type lectins administered intradermally are taken up by epidermal Langerhans cells (LCs), dermal Langerinneg DCs, and dermal Langerin+ DCs in situ. However, the relative contribution of these skin DC subsets to the induction of immune responses after Ag targeting has not been addressed in vivo. We show in this study that murine epidermal LCs and dermal DCs transport intradermally injected mAbs against the lectin receptor DEC-205/CD205 in vivo. Skin DCs targeted in situ with mAbs migrated through lymphatic vessels in steady state and inflammation. In the skin-draining lymph nodes, targeting mAbs were found in resident CD8α+ DCs and in migrating skin DCs. More than 70% of targeted DCs expressed Langerin, including dermal Langerin+ DCs and LCs. Numbers of targeted skin DCs in the nodes increased 2-3-fold when skin was topically inflamed by the TLR7 agonist imiquimod. Complete removal of the site where OVA-coupled anti–DEC-205 had been injected decreased endogenous cytotoxic responses against OVA peptide-loaded target cells by 40–50%. Surprisingly, selective ablation of all Langerin+ skin DCs in Langerin-DTR knock-in mice did not affect such responses independently of the adjuvant chosen. Thus, in cutaneous immunization strategies where Ag is targeted to DCs, Langerin+ skin DCs play a major role in transport of anti–DEC-205 mAb, although Langerinneg dermal DCs and CD8α+ DCs are sufficient to subsequent CD8+ T cell responses.
Sem Saeland - One of the best experts on this subject based on the ideXlab platform.
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structural studies of Langerin and birbeck granule a macromolecular organization model
Biochemistry, 2009Co-Authors: Michel Thepaut, Jenny Valladeau, Sem Saeland, Alessandra Nurisso, Richard A Kahn, Bertrand Arnou, Corinne Vives, Christine Ebel, Carine Monnier, Colette DezutterdambuyantAbstract:Dendritic cells, a sentinel immunity cell lineage, include different cell subsets that express various C-type lectins. For example, epidermal Langerhans cells express Langerin, and some dermal dendritic cells express DC-SIGN. Langerin is a crucial component of Birbeck granules, the Langerhans cell hallmark organelle, and may have a preventive role toward HIV, by its internalization into Birbeck granules. Since Langerin carbohydrate recognition domain (CRD) is crucial for HIV interaction and Birbeck granule formation, we produced the CRD of human Langerin and solved its structure at 1.5 A resolution. On this basis gp120 high-mannose oligosaccharide binding has been evaluated by molecular modeling. Hydrodynamic studies reveal a very elongated shape of recombinant Langerin extracellular domain (ECD). A molecular model of the Langerin ECD, integrating the CRD structure, has been generated and validated by comparison with hydrodynamic parameters. In parallel, Langerhans cells were isolated from human skin. Fro...
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expression of Langerin cd207 reveals dendritic cell heterogeneity between inbred mouse strains
Immunology, 2008Co-Authors: Vincent Flacher, Valerie Clairmoninot, Smina Aityahia, Patrizia Stoitzner, Patrice Douillard, Nikolaus Romani, Sem SaelandAbstract:Langerin/CD207 is expressed by a subset of dendritic cells (DC), the epithelial Langerhans cells. However, Langerin is also detected among lymphoid tissue DC. Here, we describe striking differences in Langerin-expressing cells between inbred mouse strains. While Langerin+ cells are observed in comparable numbers and with comparable phenotypes in the epidermis, two distinct DC subsets bear Langerin in peripheral, skin-draining lymph nodes of BALB/c mice (CD11c(high) CD8alpha(high) and CD11c(low) CD8alpha(low)), whereas only the latter subset is present in C57BL/6 mice. The CD11c(high) subset is detected in mesenteric lymph nodes and spleen of BALB/c mice, but is virtually absent from C57BL/6 mice. Similar differences are observed in other mouse strains. CD11c(low) Langerin+ cells represent skin-derived Langerhans cells, as demonstrated by their high expression of DEC-205/CD205, maturation markers, and recruitment to skin-draining lymph nodes upon imiquimod-induced inflammation. It will be of interest to determine the role of lymphoid tissue-resident compared to skin-derived Langerin+ DC.
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Expression of Langerin/CD207 reveals dendritic cell heterogeneity between inbred mouse strains.
Immunology, 2008Co-Authors: Vincent Flacher, Valérie Clair-moninot, Smina Ait-yahia, Patrizia Stoitzner, Patrice Douillard, Nikolaus Romani, Sem SaelandAbstract:Langerin/CD207 is expressed by a subset of dendritic cells (DC), the epithelial Langerhans cells. However, Langerin is also detected among lymphoid tissue DC. Here, we describe striking differences in Langerin-expressing cells between inbred mouse strains. While Langerin+ cells are observed in comparable numbers and with comparable phenotypes in the epidermis, two distinct DC subsets bear Langerin in peripheral, skin-draining lymph nodes of BALB/c mice (CD11c(high) CD8alpha(high) and CD11c(low) CD8alpha(low)), whereas only the latter subset is present in C57BL/6 mice. The CD11c(high) subset is detected in mesenteric lymph nodes and spleen of BALB/c mice, but is virtually absent from C57BL/6 mice. Similar differences are observed in other mouse strains. CD11c(low) Langerin+ cells represent skin-derived Langerhans cells, as demonstrated by their high expression of DEC-205/CD205, maturation markers, and recruitment to skin-draining lymph nodes upon imiquimod-induced inflammation. It will be of interest to determine the role of lymphoid tissue-resident compared to skin-derived Langerin+ DC.
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mouse lymphoid tissue contains distinct subsets of Langerin cd207 dendritic cells only one of which represents epidermal derived langerhans cells
Journal of Investigative Dermatology, 2005Co-Authors: Patrice Douillard, Valerie Clairmoninot, Smina Aityahia, Christoph H Tripp, Patrizia Stoitzner, Nikolaus Romani, Alexander D Mclellan, Andreas O Eggert, Sem SaelandAbstract:Langerin/CD207 is a C-type lectin associated with formation of Birbeck granules (BG) in Langerhans cells (LC). Here, we describe a monoclonal antibody (mAb 205C1) recognizing the extracellular domain of mouse Langerin. Cell-surface Langerin was detected in all epidermal LC, which presented a uniform phenotype. Two subpopulations of Langerin+ cells were identified in peripheral lymph nodes (LN). One population (subset 1) was CD11clow/+/CD8α−/low/CD11b+/CD40+/CD86+. The other population (subset 2) was CD11chigh/CD8α+/CD11blow, and lacked CD40 and CD86. Only subset 1 was fluorescein 5-isothiocyanate (FITC+) following painting onto epidermis, and the appearance of such FITC+ cells in draining LN was inhibited by pertussis toxin. Mesenteric LN, spleen, and thymus contained only a single population of Langerin+ DC, corresponding to peripheral LN subset 2. Unexpectedly, BG were absent from spleen CD8α+ DC despite expression of Langerin, and these organelles were not induced by mAb 205C1. Collectively, we demonstrate that two Langerin+ DC populations (subsets 1 and 2) co-exist in mouse lymphoid tissue. Subset 1 unequivocally identifies epidermal LC-derived DC. The distribution of subset 2 indicates a non-LC origin of these Langerin+ cells. These findings should facilitate our understanding of the role played by Langerin in lymphoid organ DC subsets.
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Mouse Lymphoid Tissue Contains Distinct Subsets of Langerin/CD207+ Dendritic Cells, Only One of Which Represents Epidermal-Derived Langerhans Cells
Journal of Investigative Dermatology, 2005Co-Authors: Patrice Douillard, Valérie Clair-moninot, Smina Ait-yahia, Christoph H Tripp, Patrizia Stoitzner, Nikolaus Romani, Alexander D Mclellan, Andreas O Eggert, Sem SaelandAbstract:Langerin/CD207 is a C-type lectin associated with formation of Birbeck granules (BG) in Langerhans cells (LC). Here, we describe a monoclonal antibody (mAb 205C1) recognizing the extracellular domain of mouse Langerin. Cell-surface Langerin was detected in all epidermal LC, which presented a uniform phenotype. Two subpopulations of Langerin+ cells were identified in peripheral lymph nodes (LN). One population (subset 1) was CD11clow/+/CD8α−/low/CD11b+/CD40+/CD86+. The other population (subset 2) was CD11chigh/CD8α+/CD11blow, and lacked CD40 and CD86. Only subset 1 was fluorescein 5-isothiocyanate (FITC+) following painting onto epidermis, and the appearance of such FITC+ cells in draining LN was inhibited by pertussis toxin. Mesenteric LN, spleen, and thymus contained only a single population of Langerin+ DC, corresponding to peripheral LN subset 2. Unexpectedly, BG were absent from spleen CD8α+ DC despite expression of Langerin, and these organelles were not induced by mAb 205C1. Collectively, we demonstrate that two Langerin+ DC populations (subsets 1 and 2) co-exist in mouse lymphoid tissue. Subset 1 unequivocally identifies epidermal LC-derived DC. The distribution of subset 2 indicates a non-LC origin of these Langerin+ cells. These findings should facilitate our understanding of the role played by Langerin in lymphoid organ DC subsets.
Ian F Hermans - One of the best experts on this subject based on the ideXlab platform.
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Langerin cd8α dendritic cells drive early cd8 t cell activation and il 12 production during systemic bacterial infection
Frontiers in Immunology, 2018Co-Authors: Troels R Petersen, Ian F Hermans, Kelly A. Prendergast, Naomi J Daniels, Joanna R. KirmanAbstract:Bloodstream infections induce considerable morbidity, high mortality and represent a significant burden of cost in health care; however, our understanding of the immune response to bacteraemia is incomplete. Langerin+ CD8alpha+ dendritic cells (DCs), residing in the marginal zone of the murine spleen, have the capacity to cross-prime CD8+ T cells and produce IL-12, both of which are important components of antimicrobial immunity. Accordingly, we hypothesised that this DC subset may be a key promoter of adaptive immune responses to blood-borne bacterial infections. Utilising mice that express the diphtheria toxin receptor under control of the Langerin promoter, we investigated the impact of depleting Langerin+ CD8alpha+ DCs in a murine model of intravenous infection with Mycobacterium bovis bacille Calmette Guerin (BCG). In the absence of Langerin+ CD8alpha+ DCs, the immune response to blood-borne BCG infection was diminished: bacterial numbers in the spleen increased, serum IL-12p40 decreased, and delayed CD8+ T cell activation, proliferation and IFN-γ production was evident. Our data revealed that Langerin+ CD8alpha+ DCs play a pivotal role in initiating CD8+ T cell responses and IL-12 production in response to bacteraemia, and may influence the early control of systemic bacterial infections.
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batf3 independent Langerin cx3cr1 cd8α splenic dcs represent a precursor for classical cross presenting cd8α dcs
Journal of Leukocyte Biology, 2014Co-Authors: Troels R Petersen, Deborah A Knight, Chingwen Tang, Taryn L Osmond, Ian F HermansAbstract:This study tests the hypothesis that CD8α(+) DCs in the spleen of mice contain an immature precursor for functionally mature, "classical" cross-presenting CD8α(+) DCs. The lymphoid tissues contain a network of phenotypically distinct DCs with unique roles in surveillance and immunity. Splenic CD8α(+) DCs have been shown to exhibit a heightened capacity for phagocytosis of cellular material, secretion of IL-12, and cross-priming of CD8(+) T cells. However, this population can be subdivided further on the basis of expression of both Langerin/CD207 and CX(3)CR1. We therefore evaluated the functional capacities of these different subsets. The CX(3)CR1(+) CD8α(+) DC subset does not express Langerin and does not exhibit the classical features above. The CX(3)CR1(-) CD8α(+) DC can be divided into Langerin-positive and negative populations, both of which express DEC205, Clec9A, and high basal levels of CD86. However, the Langerin(+) CX(3)CR1(-) CD8α(+) subset has a superior capacity for acquiring cellular material and producing IL-12 and is more susceptible to activation-induced cell death. Significantly, following purification and adoptive transfer into new hosts, the Langerin(-) CX(3)CR1(-) CD8α(+) subset survives longer, up-regulates expression of Langerin, and becomes more susceptible to activation-induced cell death. Last, in contrast to Langerin(+) CX(3)CR1(-) CD8α(+), the Langerin(-) CX(3)CR1(-) CD8α(+) are still present in Batf3(-/-) mice. We conclude that the classical attributes of CD8α(+) DC are confined primarily to the Langerin(+) CX(3)CR1(-) CD8α(+) DC population and that the Langerin(-) CX(3)CR1(-) subset represents a Batf3-independent precursor to this mature population.
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Batf3‐independent Langerin− CX3CR1− CD8α+ splenic DCs represent a precursor for classical cross‐presenting CD8α+ DCs
Journal of Leukocyte Biology, 2014Co-Authors: Troels R Petersen, Deborah A Knight, Chingwen Tang, Taryn L Osmond, Ian F HermansAbstract:This study tests the hypothesis that CD8α(+) DCs in the spleen of mice contain an immature precursor for functionally mature, "classical" cross-presenting CD8α(+) DCs. The lymphoid tissues contain a network of phenotypically distinct DCs with unique roles in surveillance and immunity. Splenic CD8α(+) DCs have been shown to exhibit a heightened capacity for phagocytosis of cellular material, secretion of IL-12, and cross-priming of CD8(+) T cells. However, this population can be subdivided further on the basis of expression of both Langerin/CD207 and CX(3)CR1. We therefore evaluated the functional capacities of these different subsets. The CX(3)CR1(+) CD8α(+) DC subset does not express Langerin and does not exhibit the classical features above. The CX(3)CR1(-) CD8α(+) DC can be divided into Langerin-positive and negative populations, both of which express DEC205, Clec9A, and high basal levels of CD86. However, the Langerin(+) CX(3)CR1(-) CD8α(+) subset has a superior capacity for acquiring cellular material and producing IL-12 and is more susceptible to activation-induced cell death. Significantly, following purification and adoptive transfer into new hosts, the Langerin(-) CX(3)CR1(-) CD8α(+) subset survives longer, up-regulates expression of Langerin, and becomes more susceptible to activation-induced cell death. Last, in contrast to Langerin(+) CX(3)CR1(-) CD8α(+), the Langerin(-) CX(3)CR1(-) CD8α(+) are still present in Batf3(-/-) mice. We conclude that the classical attributes of CD8α(+) DC are confined primarily to the Langerin(+) CX(3)CR1(-) CD8α(+) DC population and that the Langerin(-) CX(3)CR1(-) subset represents a Batf3-independent precursor to this mature population.
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Sustained in vivo depletion of splenic Langerin(+) CD8α(+) dendritic cells is well-tolerated by lang-DTREGFP mice.
Journal of Immunological Methods, 2014Co-Authors: Kelly A. Prendergast, Taryn L Osmond, Ian F Hermans, Sotaro Ochiai, Joanna R. KirmanAbstract:Abstract Splenic Langerin+ CD8α+ dendritic cells (DCs) have exhibited a critical role in cross-priming CD8+ T cell responses. To further study the roles of this DC subset, a protocol for the continuous depletion of Langerin+ CD8α+ DCs was established using the pre-existing lang-DTREGFP mouse model. Due to the fast turnover rate of splenic CD8α+ DCs, maintaining the depletion of Langerin+ CD8α+ DCs required multiple diphtheria toxin (DT) treatments. We found that prolonged treatment with DT did not cause weight loss, or neutrophilia, as reported in some DT-based depletion models. Therefore, the in vivo depletion of murine Langerin+ CD8α+ DCs can be maintained over time to analyse their function during the full course of an immune response.
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abstract b72 cd8αα Langerin dendritic cells maintain the effector cd8 t cell population after adoptive transfer
Cancer Research, 2013Co-Authors: John D Gibbins, Ian F Hermans, Troels R PetersenAbstract:Adoptive cell transfer (ACT) is a promising new area of anti-cancer therapy. The process involves the isolation of T cells from a patient's blood, in vitro stimulation of the T cells against cancer antigens, then re-infusion of the activated cells back into the patient. This process provides a population of effector CD8 T cells capable of recognizing and killing cancer cells. ACT is currently limited by the ability of the transferred cells to survive in high numbers for an extended period of time and therefore overcoming this problem is a focus to improve the efficacy of the treatment. The activation of cancer-specific CD8 T cells is dependent on the ability of dendritic cells (DCs) to acquire and present exogenous antigens on major histocompatibility complex class I (a process known as cross-presentation) for the stimulation of CD8 T cells. We have previously found a subset of splenic DCs expressing the CD8αα homodimer and the c-type lectin receptor Langerin (CD207), that have a strong ability to activate CD8 T cells by cross-presentation. This DC subset is found in the marginal zone of the spleen, is highly efficient at phagocytosing apoptotic cells from the blood, and is believed to play an important role in scanning the blood for antigens. We therefore hypothesized that CD8αα+ Langerin+ DCs influence the survival and expansion of adoptively transferred effector CD8 T cells in the blood. Within this project we have used Langerin-diphtheria toxin receptor mice, in which all Langerin-expressing cells are ablated in vivo upon injection of diphtheria toxin, to address the role of the CD8αα+ Langerin+ DC subset in maintaining the CD8 T cell population after ACT. For this purpose, we challenged mice intravenously with the T cell thymoma EG7.OVA and adoptively transferred in vitro activated OVA-specific CD8 T cells (OT-I T cells) 12 days later with or without prior Langerin-DC depletion. We found a larger population of OT-I T cells when these were transferred into an EG7.OVA bearing host when compared to mice without tumors. Interestingly, mice that were depleted of their CD8αα+ Langerin+ DCs did not develop this increase in OT-I T cell number and their absence resulted in reduced survival. Our data therefore suggest that antigen presentation by CD8αα+ Langerin+ DCs play a role in sustaining high numbers of transferred CD8 T cells after ACT, resulting in increased protection against EG7.OVA. Manipulations that increase the stimulatory capacity of this DC subset could be a way to increase the efficacy of ACT therapy. Citation Format: John David Gibbins, Ian Hermans, Troels Petersen. CD8αα+ Langerin+ dendritic cells maintain the effector CD8 T cell population after adoptive transfer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B72.
Ralph M Steinman - One of the best experts on this subject based on the ideXlab platform.
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Murine Langerin+ dermal dendritic cells prime CD8+ T cells while Langerhans cells induce cross‐tolerance
Embo Molecular Medicine, 2020Co-Authors: Vincent Flacher, Ralph M Steinman, Christoph H Tripp, Patrizia Stoitzner, David G Mairhofer, Juliana Idoyaga, Nikolaus RomaniAbstract:Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8+ T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin+ dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)-coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin+ dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8+ T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8+ T cells. Langerin/OVA combined with imiquimod could not prime CD8+ T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin+ dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8+ T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation programs.
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Murine Langerin + dermal dendritic cells prime CD8 + T cells while Langerhans cells induce
2020Co-Authors: Vincent Flacher, Ralph M Steinman, Christoph H Tripp, Patrizia Stoitzner, David G Mairhofer, Juliana Idoyaga, Nikolaus RomaniAbstract:Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8 + T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin + dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin + dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8 + T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8 + T cells. Langerin/OVA combined with imiquimod could not prime CD8 + T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin + dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8 + T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation
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murine Langerin dermal dendritic cells prime cd8 t cells while langerhans cells induce cross tolerance
Embo Molecular Medicine, 2014Co-Authors: Vincent Flacher, Ralph M Steinman, Christoph H Tripp, Patrizia Stoitzner, David G Mairhofer, Juliana Idoyaga, Nikolaus RomaniAbstract:Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8+ T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin+ dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)-coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin+ dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8+ T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8+ T cells. Langerin/OVA combined with imiquimod could not prime CD8+ T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin+ dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8+ T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation programs.
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murine Langerin dermal dendritic cells prime cd8 t cells while langerhans cells induce
2014Co-Authors: Vincent Flacher, Ralph M Steinman, Christoph H Tripp, Patrizia Stoitzner, David G Mairhofer, Juliana Idoyaga, Nikolaus RomaniAbstract:Skin dendritic cells (DCs) control the immunogenicity of cutaneously administered vaccines. Antigens targeted to DCs via the C-type lectin Langerin/CD207 are cross-presented to CD8 + T cells in vivo. We investigated the relative roles of Langerhans cells (LCs) and Langerin + dermal DCs (dDCs) in different vaccination settings. Poly(I:C) and anti-CD40 agonist antibody promoted cytotoxic responses upon intradermal immunization with ovalbumin (OVA)coupled anti-Langerin antibodies (Langerin/OVA). This correlated with CD70 upregulation in Langerin + dDCs, but not LCs. In chimeric mice where Langerin targeting was restricted to dDCs, CD8 + T-cell memory was enhanced. Conversely, providing Langerin/OVA exclusively to LCs failed to prime cytotoxicity, despite initial antigen cross-presentation to CD8 + T cells. Langerin/OVA combined with imiquimod could not prime CD8 + T cells and resulted in poor cytotoxicity in subsequent responses. This tolerance induction required targeting and maturation of LCs. Altogether, Langerin + dDCs prime long-lasting cytotoxic responses, while cross-presentation by LCs negatively influences CD8 + T-cell priming. Moreover, this highlights that DCs exposed to TLR agonists can still induce tolerance and supports the existence of qualitatively different DC maturation
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antibody to Langerin cd207 localizes large numbers of cd8α dendritic cells to the marginal zone of mouse spleen
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Juliana Idoyaga, Chae Gyu Park, Koji Suda, Nao Suda, Ralph M SteinmanAbstract:Dendritic cells (DCs) are strategically positioned to take up antigens and initiate adaptive immunity. One DC subset expresses CD8αα in mice and is specialized to capture dying cells and process antigens for MHC class I “cross-presentation.” Because CD8+ DCs also express DEC205/CD205, which is localized to splenic T cell regions, it is thought that CD8+ DCs also are restricted to T zones. Here, we used a new antibody to Langerin/CD207, which colabels isolated CD8+ CD205+ DCs, to immunolabel spleen sections. The mAb labeled discrete cells with high levels of CD11c and CD8. Surprisingly most CD207+ profiles were in marginal zones surrounding splenic white pulp nodules, and only smaller numbers were in T cell areas, where CD205 colabeling was noted. Despite a marginal zone location, CD207+ DCs lacked identifying molecules for 3 different types of macrophages, localized in proximity and, in contrast to macrophages, marginal zone DCs were poor scavengers of soluble and particulate substrates. After stimulation with microbial agonists, Langerin expression disappeared from the marginal zone at 6–12 h, but was greatly expanded in the T cell areas, and by 24–48 h, Langerin expression disappeared. Therefore, anti-Langerin antibodies localize a majority of CD8+ DCs to non-T cell regions of mouse spleen, where they are distinct from adjacent macrophages.
