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Gunilla Nordin Fredrikson - One of the best experts on this subject based on the ideXlab platform.

  • ILC2 transfers to apolipoprotein E deficient mice reduce the lipid content of atherosclerotic lesions.
    BMC immunology, 2019
    Co-Authors: Polyxeni T. Mantani, Irena Ljungcrantz, Jan Nilsson, Harry Björkbacka, Pontus Dunér, Gunilla Nordin Fredrikson
    Abstract:

    Background Expansion of type 2 innate lymphoid cells (ILC2s) in hypercholesterolaemic mice protects against atherosclerosis while different ILC2 subsets have been described (natural, inflammatory) based on their suppression of tumorigenicity 2 (ST2) and killer-cell lectin like receptor G1 (KLRG1) expression. The aim of the current study is to characterize the Interleukin 25 (IL25)-induced splenic ILC2 population (Lin−CD45+IL17RB+ICOS+IL7raintermediate) and address its direct role in experimental atherosclerosis by its adoptive transfer to hypercholesterolaemic apolipoprotein E deficient (apoE−/−) mice.

  • Interleukin 25 reduces th17 cells and inflammatory responses in human peripheral blood mononuclear cells
    Human Immunology, 2018
    Co-Authors: Polyxeni T. Mantani, Jenifer Vallejo, Irena Ljungcrantz, Jan Nilsson, Harry Björkbacka, Gunilla Nordin Fredrikson
    Abstract:

    Abstract Background The absence of Interleukin-25 (IL-25) favors the induction of Th1 and Th17 immune responses in mice. Th1 immune responses have been associated with the pathology of atherosclerosis, a lipid and inflammation driven disease of the arterial wall. Purpose of research To evaluate the effect of IL-25 on human peripheral blood mononuclear cells (hPBMCs) in the presence and absence of oxidized low density lipoprotein (oxLDL), a key player in atherosclerosis development. Principal results Human PBMCs were incubated with recombinant human IL-25 (rhIL-25) in the presence and absence of oxLDL and analyzed with flow cytometry while cytokine secretion was measured in cell culture supernatants. The IL-25 receptor, IL-17RB, was mostly expressed on T cells. Incubation of hPBMCs with IL-25 reduced the frequency of Th17 cells. Furthermore, IL-25 inhibited the release of the Th17-inducing cytokine IL-6 from dendritic cells isolated from hPBMCs indicating that the IL-25 mediated Th17 suppression may be indirect. Moreover, IL-25 reduced the secretion of the proinflammatory cytokine IFNγ from hPBMCs. OxLDL decreased IFNγ release from hPBMCs regardless of the presence or absence of IL-25. Conclusions IL-25 reduces Th1 and Th17 immune responses in hPBMCs raising the interesting possibility that IL-25 could have a protective role in human atherosclerosis.

  • Interleukin-25 reduces Th17 cells and inflammatory responses in human peripheral blood mononuclear cells
    Human immunology, 2018
    Co-Authors: Polyxeni T. Mantani, Jenifer Vallejo, Irena Ljungcrantz, Jan Nilsson, Harry Björkbacka, Gunilla Nordin Fredrikson
    Abstract:

    The absence of Interleukin-25 (IL-25) favors the induction of Th1 and Th17 immune responses in mice. Th1 immune responses have been associated with the pathology of atherosclerosis, a lipid and inflammation driven disease of the arterial wall. To evaluate the effect of IL-25 on human peripheral blood mononuclear cells (hPBMCs) in the presence and absence of oxidized low density lipoprotein (oxLDL), a key player in atherosclerosis development. Human PBMCs were incubated with recombinant human IL-25 (rhIL-25) in the presence and absence of oxLDL and analyzed with flow cytometry while cytokine secretion was measured in cell culture supernatants. The IL-25 receptor, IL-17RB, was mostly expressed on T cells. Incubation of hPBMCs with IL-25 reduced the frequency of Th17 cells. Furthermore, IL-25 inhibited the release of the Th17-inducing cytokine IL-6 from dendritic cells isolated from hPBMCs indicating that the IL-25 mediated Th17 suppression may be indirect. Moreover, IL-25 reduced the secretion of the proinflammatory cytokine IFNγ from hPBMCs. OxLDL decreased IFNγ release from hPBMCs regardless of the presence or absence of IL-25. IL-25 reduces Th1 and Th17 immune responses in hPBMCs raising the interesting possibility that IL-25 could have a protective role in human atherosclerosis. Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  • Interleukin 25 il 25 has a protective role in atherosclerosis development in the aortic arch in mice
    Journal of Biological Chemistry, 2018
    Co-Authors: Polyxeni T. Mantani, Irena Ljungcrantz, Jan Nilsson, Harry Björkbacka, Pontus Dunér, Eva Bengtsson, Lena Sundius, Gunilla Nordin Fredrikson
    Abstract:

    Atherosclerosis is a chronic inflammatory disease characterized by the entrapment of apolipoprotein B– containing lipoproteins in the arterial intima, leading to local inflammation. T helper (Th) cell 1–mediated immune responses have been associated with atherosclerosis, and the cytokine Interleukin-25 (IL-25 or IL-17E) has been reported to potentially regulate Th1 cell– and Th17 cell–related immune responses. In this study, we evaluated the effects of complete IL-25 deficiency or of a temporal IL-25 blockade on atherosclerosis development in apolipoprotein E– deficient (Apoe/) mice. Mice deficient in both apolipoprotein E and IL-25 (Apoe//IL-25/) had more Th1 cells in the spleen, along with elevated plasma levels of IL-17 and an increased release of splenic interferon- (INF-). In support of this observation, a 4-week-long treatment of young Apoe/ mice (at 10 –14 weeks of age) with an IL-25– blocking antibody increased the release of Th1/Th17-associated cytokines in the spleen. In both mouse models, these findings were associated with increased atherosclerotic plaque formation in the aortic arch. We conclude that complete IL-25 deficiency and a temporal IL-25 blockade during early plaque development aggravate atherosclerosis development in the aortic arch of Apoe/ mice, accompanied by an increase in Th1/Th17-mediated immune responses. Our finding that endogenous IL-25 has an atheroprotective role in the murine aortic arch has potential implications for atherosclerosis development and management in humans. (Less)

  • Interleukin-25 (IL-25) has a protective role in atherosclerosis development in the aortic arch in mice
    The Journal of biological chemistry, 2018
    Co-Authors: Polyxeni T. Mantani, Irena Ljungcrantz, Jan Nilsson, Harry Björkbacka, Pontus Dunér, Eva Bengtsson, Lena Sundius, Gunilla Nordin Fredrikson
    Abstract:

    Atherosclerosis is a chronic inflammatory disease characterized by the entrapment of apolipoprotein B– containing lipoproteins in the arterial intima, leading to local inflammation. T helper (Th) cell 1–mediated immune responses have been associated with atherosclerosis, and the cytokine Interleukin-25 (IL-25 or IL-17E) has been reported to potentially regulate Th1 cell– and Th17 cell–related immune responses. In this study, we evaluated the effects of complete IL-25 deficiency or of a temporal IL-25 blockade on atherosclerosis development in apolipoprotein E– deficient (Apoe/) mice. Mice deficient in both apolipoprotein E and IL-25 (Apoe//IL-25/) had more Th1 cells in the spleen, along with elevated plasma levels of IL-17 and an increased release of splenic interferon- (INF-). In support of this observation, a 4-week-long treatment of young Apoe/ mice (at 10 –14 weeks of age) with an IL-25– blocking antibody increased the release of Th1/Th17-associated cytokines in the spleen. In both mouse models, these findings were associated with increased atherosclerotic plaque formation in the aortic arch. We conclude that complete IL-25 deficiency and a temporal IL-25 blockade during early plaque development aggravate atherosclerosis development in the aortic arch of Apoe/ mice, accompanied by an increase in Th1/Th17-mediated immune responses. Our finding that endogenous IL-25 has an atheroprotective role in the murine aortic arch has potential implications for atherosclerosis development and management in humans.

Giovanni Monteleone - One of the best experts on this subject based on the ideXlab platform.

  • Interleukin-25 Negatively Controls Pathogenic Responses in the Gut
    Inflammation & allergy drug targets, 2011
    Co-Authors: Eleonora Franzè, Roberta Caruso, Angelamaria Rizzo, Francesco Pallone, Giovanni Monteleone
    Abstract:

    Although Interleukin-25 (IL-25) has been traditionally considered as a cytokine involved in T helper (Th) 2 cell-associated allergic diseases and host defence against helminthic parasites, recent studies have shown that IL-25 exerts negative effects on the initiation and progression of Th1/Th17-mediated pathologies. This later function of IL-25 is particularly evident at the gut level, where IL-25 could contribute to attenuate tissue-damaging immune responses. These new and exciting pre-clinical observations suggest that therapeutic interventions aimed at enhancing IL-25 activity could be useful in the management of patients with chronic gut inflammation.

  • The Dual Role of Interleukin-25 in the Control of Immune-Mediated Pathologies
    Current molecular medicine, 2011
    Co-Authors: Roberta Caruso, Francesco Pallone, Carmine Stolfi, D. De Nitto, Giovanni Monteleone
    Abstract:

    Interleukin-25 (IL-25) plays a key role in the initiation and expansion of T helper (Th) 2 cell-mediated immune responses, thereby contributing to allergic diseases and host defense against helminthic parasites. More recent studies have however shown that IL-25 can also control the function of non-T cells, such as antigen presenting cells and endothelial cells, and reduces Th1/Th17-mediated pathologies. These new and exciting observations reveal a broader role for IL-25 than previously anticipated, and delineate various scenarios where therapeutic interventions around IL-25 activity can be imagined.

  • Interleukin-25 fails to activate STAT6 and induce alternatively activated macrophages
    Immunology, 2010
    Co-Authors: Carmine Stolfi, Roberta Caruso, Massimiliano Sarra, Angelamaria Rizzo, Francesco Pallone, Eleonora Franzè, Daniela De Nitto, Giovanni Monteleone
    Abstract:

    Interleukin-25 (IL-25), a T helper type 2 (Th2) -related factor, inhibits the production of inflammatory cytokines by monocytes/macrophages. Since Th2 cytokines antagonize classically activated monocytes/macrophages by inducing alternatively activated macrophages (AAMs), we here assessed the effect of IL-25 on the alternative activation of human monocytes/macrophages. The Interleukins IL-25, IL-4 and IL-13 were effective in reducing the expression of inflammatory chemokines in monocytes. This effect was paralleled by induction of AAMs in cultures added with IL-4 or IL-13 but not with IL-25, regardless of whether cells were stimulated with lipopolysaccharide or interferon-γ. Moreover, pre-incubation of cells with IL-25 did not alter the ability of both IL-4 and IL-13 to induce AAMs. Both IL-4 and IL-13 activated signal transducer and activator of transcription 6 (STAT6), and silencing of this transcription factor markedly reduced the IL-4/IL-13-driven induction of AAMs. In contrast, IL-25 failed to trigger STAT6 activation. Among Th2 cytokines, only IL-25 and IL-10 were able to activate p38 mitogen-activated protein kinase. These results collectively indicate that IL-25 fails to induce AAMs and that Th2-type cytokines suppress inflammatory responses in human monocytes by activating different intracellular signalling pathways.

  • Interleukin-25: a two-edged sword in the control of immune-inflammatory responses.
    Cytokine & growth factor reviews, 2010
    Co-Authors: Giovanni Monteleone, Francesco Pallone, Thomas T. Macdonald
    Abstract:

    Interleukin-25 (IL-25), the newest member of the IL-17 cytokine family, initiates, promotes, and augments Th2 cell-mediated immune responses, thereby contributing to allergic disease and defense against helminthic parasites. More recent studies have shown that IL-25 can control the functional activity of non-T cells and suppress the initiation and progression of immune-mediated pathologies such as endotoxemia, colitis, experimental autoimmune encephalomyelitis, and diabetes. Taken together with the fact that IL-17 family members can form homo and heterodimers with different functions, the IL-17 family encapsulates the subtle pro and anti-inflammatory function of cytokines, which need to be understood before anti-cytokine therapy can be exploited rationally in the clinic.

  • Interleukin-25 Inhibits Interleukin-12 Production and Th1 Cell-Driven Inflammation in the Gut
    Gastroenterology, 2009
    Co-Authors: Roberta Caruso, Massimiliano Sarra, Angelamaria Rizzo, Daniele Fina, Massimo Fantini, Francesco Pallone, Thomas T. Macdonald, Carmine Stolfi, Giovanni Monteleone
    Abstract:

    Background & Aims During the pathogenesis of Crohn's disease (CD), Interleukin (IL)-12, a cytokine produced by mucosal CD14 + monocyte-like cells, promotes tissue-damaging T helper cell (Th) 1-mediated inflammation through mechanisms that are not fully understood. IL-25 promotes Th2 cell responses by activating major histocompatibility complex class II-positive non-T and non-B cells. Because Th1 and Th2 cells, and the cytokines they release, are often mutually antagonistic, we examined whether IL-25 affects IL-12 production or Th1 cell-mediated inflammation in the gut. Methods Studies were performed using colonic samples from patients and mice with peptidoglycan (PGN)-, 2,4,6-trinitrobenzenesulphonic acid (TNBS)-, or oxazolone-induced colitis. IL-25 receptor (IL-25R) levels were evaluated in intestinal lamina propria mononuclear cells by flow cytometry, and IL-25 levels were measured by real-time polymerase chain reaction, immunoblotting, and immunohistochemistry. Mucosal CD14 + cells from patients with CD were incubated with IL-25 and/or lipopolysaccharide or PGN. Mice were injected with IL-25, and some mice first received injections of an IL-13 blocking antibody. Cytokines were quantified by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results CD14 + cells from the mucosa of CD patients expressed IL-25R and responded to IL-25 by decreasing the synthesis of IL-12 and IL-23. IL-25 prevented PGN-induced colitis in mice. IL-25 induced IL-13 production in the colon, but IL-13 was not required for suppression of PGN colitis. IL-25 ameliorated TNBS- and oxazolone-colitis. Patients with CD or ulcerative colitis produced significantly less IL-25 compared with controls. Conclusions IL-25 inhibits CD14 + cell-derived cytokines and experimental colitis. IL-25 could be a useful treatment of CD and ulcerative colitis.

Sun Ying - One of the best experts on this subject based on the ideXlab platform.

  • distinct sustained structural and functional effects of Interleukin 33 and Interleukin 25 on the airways in a murine asthma surrogate
    Immunology, 2015
    Co-Authors: Wei Wang, Ping Huang, Qian Zhang, Xiujuan Yao, Jingjing Wang, Kewu Huang, C J Corrigan, Sun Ying
    Abstract:

    Interleukin-25 (IL-25) and IL-33, which belong to distinct cytokine families, induce and promote T helper type 2 airway inflammation. Both cytokines probably play a role in asthma, but there is a lack of direct evidence to clarify distinctions between their functions and how they might contribute to distinct 'endotypes' of disease. To address this, we made a direct comparison of the effects of IL-25 and IL-33 on airway inflammation and physiology in our established murine asthma surrogate, which involves per-nasal, direct airway challenge. Intranasal challenge with IL-33 or IL-25 induced inflammatory cellular infiltration, collagen deposition, airway smooth muscle hypertrophy, angiogenesis and airway hyper-responsiveness, but neither increased systemic production of IgE or IgG1. Compared with that of IL-25, the IL-33-induced response was characterized by more sustained laying down of extracellular matrix protein, neoangiogenesis, T helper type 2 cytokine expression and elevation of tissue damping. Hence, both IL-25 and IL-33 may contribute significantly and independently to asthma 'endotypes' when considering molecular targets for the treatment of human disease.

  • elevations in t helper 2 initiating cytokines Interleukin 33 Interleukin 25 and thymic stromal lymphopoietin in lesional skin from chronic spontaneous idiopathic urticaria
    British Journal of Dermatology, 2015
    Co-Authors: A. B. Kay, Peter Clark, Marcus Maurer, Sun Ying
    Abstract:

    Summary Background The mechanism of wealing in chronic spontaneous urticaria (CSU) is largely unknown. We previously demonstrated increased expression of T-helper 2 [Interleukin (IL)-4 and IL-5] cytokines in skin biopsies from CSU. This suggested that Th2-initiating cytokines [IL-33, IL-25 and thymic stromal lymphopoietin (TSLP)], released through innate immune mechanisms, may play a role in pathogenesis. Objectives To identify Th2-initiating cytokines in lesional and nonlesional skin from patients with CSU and to compare the results with a control group. Methods Paired biopsies (one from a 4–8 h spontaneous weal and one from uninvolved skin) were taken from eight patients with CSU and nine control subjects, and studied by immunohistochemistry and confocal microscopy. Results There were increases in IL-4+ and IL-5+ cells in lesional skin vs. controls (P = 0·03 and P < 0·001, respectively) and marked elevations in the numbers of IL-33+, IL-25+ and TSLP+ cells in the dermis of lesional skin vs. both nonlesional skin (P = 0·002, P = 0·01 and P = 0·04, respectively) and controls (P = 0·001, P < 0·001 and P = 0·005, respectively). There was also a correlation between the numbers of IL-33+ and IL-25+ cells (r = 0·808, P = 0·015). IL-33 localized to CD31+ endothelial cells, CD90+ fibroblasts, CD68+ macrophages and tryptase+ mast cells, whereas IL-25 was expressed by epithelial cells, mast cells and major basic protein-positive eosinophils. IL-33 and IL-25 were constitutively expressed in the epidermis of both controls and patients with CSU. Conclusions Increased expression of Th2-initiating cytokines in lesional skin in CSU suggests that innate pathways might play a role in the mechanism of wealing. As Th2-initiating cytokines play a role in mast cell activation, inflammation and vascular leakage in CSU, these findings may also have therapeutic implications.

  • Elevations in T-helper-2-initiating cytokines (Interleukin-33, Interleukin-25 and thymic stromal lymphopoietin) in lesional skin from chronic spontaneous (‘idiopathic’) urticaria
    The British journal of dermatology, 2015
    Co-Authors: A. B. Kay, Peter Clark, Marcus Maurer, Sun Ying
    Abstract:

    The mechanism of wealing in chronic spontaneous urticaria (CSU) is largely unknown. We previously demonstrated increased expression of T-helper 2 [Interleukin (IL)-4 and IL-5] cytokines in skin biopsies from CSU. This suggested that Th2-initiating cytokines [IL-33, IL-25 and thymic stromal lymphopoietin (TSLP)], released through innate immune mechanisms, may play a role in pathogenesis. To identify Th2-initiating cytokines in lesional and nonlesional skin from patients with CSU and to compare the results with a control group. Paired biopsies (one from a 4-8 h spontaneous weal and one from uninvolved skin) were taken from eight patients with CSU and nine control subjects, and studied by immunohistochemistry and confocal microscopy. There were increases in IL-4(+) and IL-5(+) cells in lesional skin vs. controls (P = 0·03 and P < 0·001, respectively) and marked elevations in the numbers of IL-33(+), IL-25(+) and TSLP(+) cells in the dermis of lesional skin vs. both nonlesional skin (P = 0·002, P = 0·01 and P = 0·04, respectively) and controls (P = 0·001, P < 0·001 and P = 0·005, respectively). There was also a correlation between the numbers of IL-33(+) and IL-25(+) cells (r = 0·808, P = 0·015). IL-33 localized to CD31(+) endothelial cells, CD90(+) fibroblasts, CD68(+) macrophages and tryptase(+) mast cells, whereas IL-25 was expressed by epithelial cells, mast cells and major basic protein-positive eosinophils. IL-33 and IL-25 were constitutively expressed in the epidermis of both controls and patients with CSU. Increased expression of Th2-initiating cytokines in lesional skin in CSU suggests that innate pathways might play a role in the mechanism of wealing. As Th2-initiating cytokines play a role in mast cell activation, inflammation and vascular leakage in CSU, these findings may also have therapeutic implications. © 2014 British Association of Dermatologists.

Sven Hendrix - One of the best experts on this subject based on the ideXlab platform.

  • Interleukin-25 is detrimental for recovery after spinal cord injury in mice
    Journal of neuroinflammation, 2016
    Co-Authors: Dearbhaile Dooley, Evi Lemmens, Peter Ponsaerts, Sven Hendrix
    Abstract:

    The cytokine, Interleukin (IL)-25, is thought to be critically involved in inducing a type 2 immune response which may contribute to regeneration after central nervous system (CNS) trauma. We investigated whether applying recombinant IL-25, locally or systemically, in a mouse model of spinal cord injury (SCI) improves functional and histological recovery. Repeated systemic administration of IL-25 did not influence functional recovery following SCI. In contrast, a single local administration of IL-25 significantly worsened locomotor outcome, which was evident from a decreased Basso mouse scale (BMS) score compared with phosphate-buffered saline (PBS)-treated controls. This was accompanied by a significant increase in lesion size, demyelination, and T helper cell infiltration. These data show for the first time that IL-25 is either ineffective when applied systemically or detrimental to spinal cord recovery when applied locally. Our findings question the potential neuroprotective role of IL-25 following CNS trauma.

  • Interleukin 25 is detrimental for recovery after spinal cord injury in mice
    Journal of Neuroinflammation, 2016
    Co-Authors: Dearbhaile Dooley, Evi Lemmens, Peter Ponsaerts, Sven Hendrix
    Abstract:

    Background The cytokine, Interleukin (IL)-25, is thought to be critically involved in inducing a type 2 immune response which may contribute to regeneration after central nervous system (CNS) trauma. We investigated whether applying recombinant IL-25, locally or systemically, in a mouse model of spinal cord injury (SCI) improves functional and histological recovery.

Polyxeni T. Mantani - One of the best experts on this subject based on the ideXlab platform.

  • ILC2 transfers to apolipoprotein E deficient mice reduce the lipid content of atherosclerotic lesions.
    BMC immunology, 2019
    Co-Authors: Polyxeni T. Mantani, Irena Ljungcrantz, Jan Nilsson, Harry Björkbacka, Pontus Dunér, Gunilla Nordin Fredrikson
    Abstract:

    Background Expansion of type 2 innate lymphoid cells (ILC2s) in hypercholesterolaemic mice protects against atherosclerosis while different ILC2 subsets have been described (natural, inflammatory) based on their suppression of tumorigenicity 2 (ST2) and killer-cell lectin like receptor G1 (KLRG1) expression. The aim of the current study is to characterize the Interleukin 25 (IL25)-induced splenic ILC2 population (Lin−CD45+IL17RB+ICOS+IL7raintermediate) and address its direct role in experimental atherosclerosis by its adoptive transfer to hypercholesterolaemic apolipoprotein E deficient (apoE−/−) mice.

  • Interleukin 25 reduces th17 cells and inflammatory responses in human peripheral blood mononuclear cells
    Human Immunology, 2018
    Co-Authors: Polyxeni T. Mantani, Jenifer Vallejo, Irena Ljungcrantz, Jan Nilsson, Harry Björkbacka, Gunilla Nordin Fredrikson
    Abstract:

    Abstract Background The absence of Interleukin-25 (IL-25) favors the induction of Th1 and Th17 immune responses in mice. Th1 immune responses have been associated with the pathology of atherosclerosis, a lipid and inflammation driven disease of the arterial wall. Purpose of research To evaluate the effect of IL-25 on human peripheral blood mononuclear cells (hPBMCs) in the presence and absence of oxidized low density lipoprotein (oxLDL), a key player in atherosclerosis development. Principal results Human PBMCs were incubated with recombinant human IL-25 (rhIL-25) in the presence and absence of oxLDL and analyzed with flow cytometry while cytokine secretion was measured in cell culture supernatants. The IL-25 receptor, IL-17RB, was mostly expressed on T cells. Incubation of hPBMCs with IL-25 reduced the frequency of Th17 cells. Furthermore, IL-25 inhibited the release of the Th17-inducing cytokine IL-6 from dendritic cells isolated from hPBMCs indicating that the IL-25 mediated Th17 suppression may be indirect. Moreover, IL-25 reduced the secretion of the proinflammatory cytokine IFNγ from hPBMCs. OxLDL decreased IFNγ release from hPBMCs regardless of the presence or absence of IL-25. Conclusions IL-25 reduces Th1 and Th17 immune responses in hPBMCs raising the interesting possibility that IL-25 could have a protective role in human atherosclerosis.

  • Interleukin-25 reduces Th17 cells and inflammatory responses in human peripheral blood mononuclear cells
    Human immunology, 2018
    Co-Authors: Polyxeni T. Mantani, Jenifer Vallejo, Irena Ljungcrantz, Jan Nilsson, Harry Björkbacka, Gunilla Nordin Fredrikson
    Abstract:

    The absence of Interleukin-25 (IL-25) favors the induction of Th1 and Th17 immune responses in mice. Th1 immune responses have been associated with the pathology of atherosclerosis, a lipid and inflammation driven disease of the arterial wall. To evaluate the effect of IL-25 on human peripheral blood mononuclear cells (hPBMCs) in the presence and absence of oxidized low density lipoprotein (oxLDL), a key player in atherosclerosis development. Human PBMCs were incubated with recombinant human IL-25 (rhIL-25) in the presence and absence of oxLDL and analyzed with flow cytometry while cytokine secretion was measured in cell culture supernatants. The IL-25 receptor, IL-17RB, was mostly expressed on T cells. Incubation of hPBMCs with IL-25 reduced the frequency of Th17 cells. Furthermore, IL-25 inhibited the release of the Th17-inducing cytokine IL-6 from dendritic cells isolated from hPBMCs indicating that the IL-25 mediated Th17 suppression may be indirect. Moreover, IL-25 reduced the secretion of the proinflammatory cytokine IFNγ from hPBMCs. OxLDL decreased IFNγ release from hPBMCs regardless of the presence or absence of IL-25. IL-25 reduces Th1 and Th17 immune responses in hPBMCs raising the interesting possibility that IL-25 could have a protective role in human atherosclerosis. Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  • Interleukin 25 il 25 has a protective role in atherosclerosis development in the aortic arch in mice
    Journal of Biological Chemistry, 2018
    Co-Authors: Polyxeni T. Mantani, Irena Ljungcrantz, Jan Nilsson, Harry Björkbacka, Pontus Dunér, Eva Bengtsson, Lena Sundius, Gunilla Nordin Fredrikson
    Abstract:

    Atherosclerosis is a chronic inflammatory disease characterized by the entrapment of apolipoprotein B– containing lipoproteins in the arterial intima, leading to local inflammation. T helper (Th) cell 1–mediated immune responses have been associated with atherosclerosis, and the cytokine Interleukin-25 (IL-25 or IL-17E) has been reported to potentially regulate Th1 cell– and Th17 cell–related immune responses. In this study, we evaluated the effects of complete IL-25 deficiency or of a temporal IL-25 blockade on atherosclerosis development in apolipoprotein E– deficient (Apoe/) mice. Mice deficient in both apolipoprotein E and IL-25 (Apoe//IL-25/) had more Th1 cells in the spleen, along with elevated plasma levels of IL-17 and an increased release of splenic interferon- (INF-). In support of this observation, a 4-week-long treatment of young Apoe/ mice (at 10 –14 weeks of age) with an IL-25– blocking antibody increased the release of Th1/Th17-associated cytokines in the spleen. In both mouse models, these findings were associated with increased atherosclerotic plaque formation in the aortic arch. We conclude that complete IL-25 deficiency and a temporal IL-25 blockade during early plaque development aggravate atherosclerosis development in the aortic arch of Apoe/ mice, accompanied by an increase in Th1/Th17-mediated immune responses. Our finding that endogenous IL-25 has an atheroprotective role in the murine aortic arch has potential implications for atherosclerosis development and management in humans. (Less)

  • Interleukin-25 (IL-25) has a protective role in atherosclerosis development in the aortic arch in mice
    The Journal of biological chemistry, 2018
    Co-Authors: Polyxeni T. Mantani, Irena Ljungcrantz, Jan Nilsson, Harry Björkbacka, Pontus Dunér, Eva Bengtsson, Lena Sundius, Gunilla Nordin Fredrikson
    Abstract:

    Atherosclerosis is a chronic inflammatory disease characterized by the entrapment of apolipoprotein B– containing lipoproteins in the arterial intima, leading to local inflammation. T helper (Th) cell 1–mediated immune responses have been associated with atherosclerosis, and the cytokine Interleukin-25 (IL-25 or IL-17E) has been reported to potentially regulate Th1 cell– and Th17 cell–related immune responses. In this study, we evaluated the effects of complete IL-25 deficiency or of a temporal IL-25 blockade on atherosclerosis development in apolipoprotein E– deficient (Apoe/) mice. Mice deficient in both apolipoprotein E and IL-25 (Apoe//IL-25/) had more Th1 cells in the spleen, along with elevated plasma levels of IL-17 and an increased release of splenic interferon- (INF-). In support of this observation, a 4-week-long treatment of young Apoe/ mice (at 10 –14 weeks of age) with an IL-25– blocking antibody increased the release of Th1/Th17-associated cytokines in the spleen. In both mouse models, these findings were associated with increased atherosclerotic plaque formation in the aortic arch. We conclude that complete IL-25 deficiency and a temporal IL-25 blockade during early plaque development aggravate atherosclerosis development in the aortic arch of Apoe/ mice, accompanied by an increase in Th1/Th17-mediated immune responses. Our finding that endogenous IL-25 has an atheroprotective role in the murine aortic arch has potential implications for atherosclerosis development and management in humans.