The Experts below are selected from a list of 200790 Experts worldwide ranked by ideXlab platform
Toshinori Nakayama - One of the best experts on this subject based on the ideXlab platform.
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Menin Controls the Memory Th2 Cell Function by Maintaining the Epigenetic Integrity of Th2 Cells.
Journal of immunology (Baltimore Md. : 1950), 2017Co-Authors: Atsushi Onodera, Miki Kato, Masahiro Kiuchi, Kota Kokubo, Tomohiro Ogino, Shu Horiuchi, Urara Kanai, Kiyoshi Hirahara, Toshinori NakayamaAbstract:Posttranslational modifications of histones are well-established epigenetic modifications that play an important role in gene expression and regulation. These modifications are partly mediated by the Trithorax group (TrxG) complex, which regulates the induction or maintenance of gene transcription. We investigated the role of Menin, a component of the TrxG complex, in the acquisition and maintenance of Th2 Cell identity using T Cell-specific Menin-deficient mice. Our gene expression analysis revealed that Menin was involved in the maintenance of the high expression of the previously identified Th2-specific genes rather than the induction of these genes. This result suggests that Menin plays a role in the maintenance of Th2 Cell identity. Menin directly bound to the Gata3 gene locus, and this Menin-Gata3 axis appeared to form a core unit of the Th2-specific gene regulatory network. Consistent with the phenotype of Menin-deficient Th2 Cells observed in vitro, Menin deficiency resulted in the attenuation of effector Th2 Cell-induced airway inflammation. In addition, in memory Th2 (mTh2) Cells, Menin was found to play an important role in the maintenance of the expression of Th2-specific genes, including Gata3, Il4, and Il13 Consequently, Menin-deficient mTh2 Cells showed an impaired ability to recruit eosinophils to the lung, resulting in the attenuation of mTh2 Cell-induced airway inflammation. This study confirmed the critical role of Menin in Th2 Cell-mediated immune responses.
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Th2 Cells in Health and Disease.
Annual review of immunology, 2016Co-Authors: Toshinori Nakayama, Hiroyuki Hosokawa, Yusuke Endo, Atsushi Onodera, Damon J. Tumes, Kiyoshi Hirahara, Kenta Shinoda, Yoshitaka OkamotoAbstract:Helper T (Th) Cell subsets direct immune responses by producing signature cytokines. Th2 Cells produce IL-4, IL-5, and IL-13, which are important in humoral immunity and protection from helminth infection and are central to the pathogenesis of many allergic inflammatory diseases. Molecular analysis of Th2 Cell differentiation and maintenance of function has led to recent discoveries that have refined our understanding of Th2 Cell biology. Epigenetic regulation of Gata3 expression by chromatin remodeling complexes such as Polycomb and Trithorax is crucial for maintaining Th2 Cell identity. In the context of allergic diseases, memory-type pathogenic Th2 Cells have been identified in both mice and humans. To better understand these disease-driving Cell populations, we have developed a model called the pathogenic Th population disease induction model. The concept of defined subsets of pathogenic Th Cells may spur new, effective strategies for treating intractable chronic inflammatory disorders.
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Memory Th1/Th2 Cell generation controlled by Schnurri-2.
Advances in experimental medicine and biology, 2010Co-Authors: Toshinori Nakayama, Motoko Y. KimuraAbstract:Schnurri (Shn) is a large zinc-finger containing protein, which plays a critical role in Cell growth, signal transduction and lymphocyte development. There are three orthologues (Shn-1, Shn-2 and Shn-3) in vertebrates. In Shn-2-deficient mice, the activation of NF-κB in CD4 T Cells is upregulated and their ability to differentiate into Th2 Cells is enhanced in part through the increased expression of GATA3. Shn-2 is found to compete with p50 NF- κB for binding to a consensus NF-κB motif and inhibit the NF-κB-driven promoter activity. In addition, Th2-driven allergic airway inflammation was enhanced in Shn-2-deficient mice. Therefore, Shn-2 appears to negatively control the differentiation of Th2 Cells and Th2 responses through the repression of NF-κB function. Memory Th1/Th2 Cells are not properly generated from Shn-2-deficient effector Th1/Th2 Cells. The expression levels of CD69 and the number of apoptotic Cells are selectively increased in Shn-2-deficient Th1/Th2 Cells when they are transferred into syngeneic host animals, in which memory Th1/Th2 Cells are generated within a month. In addition, an increased susceptibility to apoptotic Cell death is also observed in vitro accompanied with the increased expression of FasL, one of the NF-κB-dependent genes. Th2 effector Cells overexpressing the p65 subunit of NF-κB demonstrate a decreased Cell survival particularly in the lymph node. These results indicate that Shn-2-mediated repression of NF-κB is required for Cell survival and the successful generation of memory Th1/Th2 Cells. This may point to the possibility that after antigen clearance the recovery of the quiescent state in effector Th Cells is required for the generation of memory Th Cells. A repressor molecule Shn-2 plays an important role in this process.
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Gfi1-mediated Stabilization of GATA3 Protein Is Required for Th2 Cell Differentiation
The Journal of biological chemistry, 2008Co-Authors: Ryo Shinnakasu, Hiroyuki Hosokawa, Masakatsu Yamashita, Makoto Kuwahara, Akihiro Hasegawa, Shinichiro Motohashi, Toshinori NakayamaAbstract:Abstract The differentiation of naive CD4 T Cells into Th2 Cells requires the T Cell receptor-mediated activation of the ERK MAPK cascade. Little is known, however, in regard to how the ERK MAPK cascade regulates Th2 Cell differentiation. We herein identified Gfi1 (growth factor independent-1) as a downstream target of the ERK MAPK cascade for Th2 Cell differentiation. In the absence of Gfi1, interleukin-5 production and the change of histone modification at the interleukin-5 gene locus were severely impaired. Furthermore, the interferon γ gene showed a striking activation in the Gfi1–/– Th2 Cells. An enhanced ubiquitin/proteasome-dependent degradation of GATA3 protein was observed in Gfi1–/– Th2 Cells, and the overexpression of GATA3 eliminated the defect of Th2 Cell function in Gfi1-deficient Th2 Cells. These data suggest that the T Cell receptor-mediated induction of Gfi1 controls Th2 Cell differentiation through the regulation of GATA3 protein stability.
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Initiation and maintenance of Th2 Cell identity.
Current opinion in immunology, 2008Co-Authors: Toshinori Nakayama, Masakatsu YamashitaAbstract:T helper type 2 (Th2) Cells produce IL-4, IL-5, and IL-13 and play an important role in humoral immunity and allergic reactions. During Th2 Cell differentiation, naive CD4 T Cells acquire 'Th2 Cell identity', that is, the capability to produce selectively a large amount of Th2 cytokines. Th2 Cell identity is maintained in memory Th2 Cells. Significant advances in understanding of the molecular requirement for these processes have been made. The expression of GATA3, a master transcription factor for Th2 Cell differentiation, is uniquely regulated by several distinct mechanisms. Molecular analyses of memory Th2 Cells revealed that Cell survival and the maintenance of Th2 Cell function are epigenetically regulated by various nuclear factors, including Polycomb and Trithorax molecules.
Andrew N. J. Mckenzie - One of the best experts on this subject based on the ideXlab platform.
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Group 2 innate lymphoid Cells collaborate with dendritic Cells to potentiate memory Th2 Cell responses.
Journal of Immunology, 2016Co-Authors: Timotheus Y.f. Halim, You Yi Hwang, Seth T. Scanlon, Habib Zaghouani, Natalio Garbi, Padraic G. Fallon, Andrew N. J. MckenzieAbstract:Rapid memory CD4+ T helper 2 (Th2) Cell activation during allergic inflammation requires their recruitment into the affected tissue. Tissue-resident innate immune Cells such as dendritic Cells (DC) are essential for orchestrating local memory Th2 Cell responses. We now know that tissue-resident group 2 innate lymphoid Cells (ILC2) are an important innate source of type-2 cytokines in barrier sites. However, it is currently not known if ILC2 remain functionally important after the generation of adaptive Th2 Cells. Here we demonstrate that group 2 innate lymphoid Cells (ILC2) play a critical role in memory Th2 Cell responses. By targeted ILC2 depletion, using ILC2-specific diphtheria toxin receptor expressing iCOS-T mice, we show a profound impairment in Th2 Cell localization to the lungs and skin of sensitized mice after allergen re-challenge. Mechanistically, ILC2-derived IL-13 is critical for eliciting IRF4+CD11b+CD103− DCs to produce the Th2 Cell-attracting chemokine CCL17. Consequently, the sentinel function of DCs is contingent on ILC2s for the generation of an efficient memory Th2 Cell response. These results elucidate a key new innate mechanism in the regulation of the adaptive memory immune response to allergens.
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Group 2 innate lymphoid Cells license dendritic Cells to potentiate memory Th2 Cell responses
Nature immunology, 2015Co-Authors: Timotheus Y.f. Halim, You Yi Hwang, Seth T. Scanlon, Habib Zaghouani, Natalio Garbi, Padraic G. Fallon, Andrew N. J. MckenzieAbstract:Rapid activation of memory CD4(+) T helper 2 (Th2) Cells during allergic inflammation requires their recruitment into the affected tissue. Here we demonstrate that group 2 innate lymphoid (ILC2) Cells have a crucial role in memory Th2 Cell responses, with targeted depletion of ILC2 Cells profoundly impairing Th2 Cell localization to the lungs and skin of sensitized mice after allergen re-challenge. ILC2-derived interleukin 13 (IL-13) is critical for eliciting production of the Th2 Cell-attracting chemokine CCL17 by IRF4(+)CD11b(+)CD103(-) dendritic Cells (DCs). Consequently, the sentinel function of DCs is contingent on ILC2 Cells for the generation of an efficient memory Th2 Cell response. These results elucidate a key innate mechanism in the regulation of the immune memory response to allergens.
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group 2 innate lymphoid Cells are critical for the initiation of adaptive t helper 2 Cell mediated allergic lung inflammation
Immunity, 2014Co-Authors: Timotheus Y.f. Halim, Andrew N. J. Mckenzie, Catherine A Steer, Laura Matha, Matthew J Gold, Itziar Martinezgonzalez, Kelly M Mcnagny, Fumio TakeiAbstract:Naive CD4+ T Cell differentiation into distinct subsets of T helper (Th) Cells is a pivotal process in the initiation of the adaptive immune response. Allergens predominantly stimulate Th2 Cells, causing allergic inflammation. However, why allergens induce Th2 Cell differentiation is not well understood. Here we show that group 2 innate lymphoid Cells (ILC2s) are required to mount a robust Th2 Cell response to the protease-allergen papain. Intranasal administration of papain stimulated ILC2s and Th2 Cells, causing allergic lung inflammation and elevated immunoglobulin E titers. This process was severely impaired in ILC2-deficient mice. Whereas interleukin-4 (IL-4) was dispensable for papain-induced Th2 Cell differentiation, ILC2-derived IL-13 was critical as it promoted migration of activated lung dendritic Cells into the draining lymph node where they primed naive T Cells to differentiate into Th2 Cells. Papain-induced ILC2 activation and Th2 Cell differentiation was IL-33-dependent, suggesting a common pathway in the initiation of Th2 Cell responses to allergen.
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a distinct role for interleukin 13 in Th2 Cell mediated immune responses
Current Biology, 1998Co-Authors: Grahame James Mckenzie, Allison J Bancroft, Richard K Grencis, Andrew N. J. MckenzieAbstract:Abstract Immune responses elicited by allergic reactions and parasitic worm infections are characterised by the induction of T helper 2 (Th2) Cells. These Cells secrete cytokines such as interleukin-4 (IL-4), IL-5 and IL-13, which induce the production of immunoglobulin E (IgE) and eosinophils [1,2]. Previous studies using gastrointestinal nematodes to elucidate the role of Th2-Cell-mediated immune responses have demonstrated a causal relationship between T Cells and worm expulsion (reviewed in [3]). Although it has been proposed that IL-4 played a central role in these responses, recent studies demonstrated that IL-4 −/− mice expel the parasitic gastrointestinal nematode Nippostrongylus brasiliensis normally [4], suggesting that another T-Cell mediator is required for efficient worm clearance. Using IL-13 −/− mice, we have demonstrated that, unlike wild-type and IL-4 −/− mice, the IL-13 −/− animals failed to clear N. brasiliensis infections efficiently, despite developing a robust Th2-like cytokine response to infection. Furthermore, treatment of the IL-13 −/− mice with exogenous IL-13 resulted in a reduction in the numbers of worms recovered. The IL-13 −/− animals also failed to generate the goblet Cell hyperplasia that normally occurs coincident with worm expulsion. This observation may link IL-13 with the production of intestinal mucus which is believed to facilitate worm expulsion. These data support a unique role for IL-13 in Th2-Cell-mediated immune responses and demonstrate that IL-13 and IL-4 are not redundant.
Itsuo Iwamoto - One of the best experts on this subject based on the ideXlab platform.
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STAT6 inhibits T-bet-independent Th1 Cell differentiation
Biochemical and Biophysical Research Communications, 2009Co-Authors: Tomohiro Tamachi, Yuko Maezawa, Akira Suto, Michio Fujiwara, Shin-ichiro Kagami, Hiroaki Takatori, Norihiko Watanabe, Itsuo Iwamoto, Koichi Hirose, Hiroshi NakajimaAbstract:Abstract STAT6 plays critical roles in Th2 Cell differentiation, whereas STAT4 and T-bet are important for Th1 Cell differentiation. However, it is still largely unknown about the cross talk of these transcription factors during Th1/Th2 Cell differentiation. To further address the regulatory mechanisms underlying Th1/Th2 Cell differentiation, we generated the mice lacking both STAT6 and T-bet (STAT6−/−T-bet−/− mice). Importantly, although Th2 Cell differentiation was severely and similarly decreased in STAT6−/−T-bet−/− mice and STAT6−/− mice, Th1 Cell differentiation was rescued in part in STAT6−/−T-bet−/− mice as compared with that in T-bet−/− mice. While no significant difference was observed in the expression of IL-12Rβ2 and STAT4 between STAT6−/−T-bet−/− CD4+ T Cells and T-bet−/− CD4+ T Cells, IL-12-induced STAT4 phosphorylation was increased in STAT6−/−T-bet−/− CD4+ T Cells as compared with that in T-bet−/− CD4+ T Cells. These results indicate that STAT6 inhibits T-bet-independent Th1 Cell differentiation by suppressing IL-12-STAT4 signaling.
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indispensable role of stat5a in stat6 independent Th2 Cell differentiation and allergic airway inflammation
Journal of Immunology, 2005Co-Authors: Hiroaki Takatori, Akira Suto, Tomohiro Tamachi, Shin-ichiro Kagami, Yasushi Saito, Kotaro Suzuki, Koichi Hirose, Hiroshi Nakajima, Itsuo IwamotoAbstract:It is well-recognized that Stat6 plays a critical role in Th2 Cell differentiation and the induction of allergic inflammation. We have previously shown that Stat5a is also required for Th2 Cell differentiation and allergic airway inflammation. However, it is the relative importance and redundancy of Stat6 and Stat5a in Th2 Cell differentiation and allergic airway inflammation are unknown. In this study we addressed these issues by comparing Stat5a-deficient (Stat5a −/− ) mice, Stat6 −/− mice, and Stat5a- and Stat6 double-deficient (Stat5a −/− Stat6 −/− ) mice on the same genetic background. Th2 Cell differentiation was severely decreased in Stat6 −/− CD4 + T Cells, but Stat6-independent Th2 Cell differentiation was still significantly observed in Stat6 −/− CD4 + T Cells. However, even in the Th2-polarizing condition (IL-4 plus anti-IFN-γ mAb), no Th2 Cells developed in Stat5a −/− Stat6 −/− CD4 + T Cells. Moreover, Ag-induced eosinophil and lymphocyte recruitment in the airways was severely decreased in Stat5a −/− Stat6 −/− mice compared with that in Stat6 −/− mice. These results indicate that Stat5a plays an indispensable role in Stat6-independent Th2 Cell differentiation and subsequent Th2 Cell-mediated allergic airway inflammation.
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IgE-dependent enhancement of Th2 Cell-mediated allergic inflammation in the airways
Clinical and experimental immunology, 2004Co-Authors: Yuko Maezawa, Akira Suto, Yasushi Saito, Hiroshi Nakajima, Yohei Seto, Kotaro Kumano, S. Kubo, Hajime Karasuyama, Itsuo IwamotoAbstract:SUMMARY T helper 2 (Th2) Cell-derived cytokines, including interleukin (IL)-4, IL-5 and IL-13, play important roles in causing allergic airway inflammation. In contrast to Th2 Cells, however, the role of IgE and mast Cells in inducing allergic airway inflammation is not understood fully. In the present study, we addressed this point using transgenic mice expressing trinitrophenyl (TNP)-specific IgE (TNP‐IgE mice), which enable us to investigate the role of IgE without the influence of antigen-specific T Cell activation and other immunoglobulins. When the corresponding antigen, TNP‐BSA, was administered intranasally to TNP‐IgE mice, a large number of CD4 + T Cells were recruited into the airways. In contrast, TNP‐BSA administration did not induce eosinophil recruitment into the airways or airway hyperreactivity. Furthermore, when ovalbumin (OVA)-specific Th2 Cells were transferred to TNP‐IgE mice and the mice were challenged with inhaled OVA, TNP‐BSA administration increased OVA-specific T Cell recruitment and then enhanced Th2 Cell-mediated eosinophil recruitment into the airways. These results indicate that IgE-induced mast Cell activation principally induces CD4 + T Cell recruitment into the airways and thus plays an important role in enhancing Th2 Cell-mediated eosinophilic airway inflammation by recruiting Th2 Cells into the site of allergic inflammation.
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Role of IgE in Th2 Cell-mediated allergic airway inflammation.
International Archives of Allergy and Immunology, 2003Co-Authors: Yuko Maezawa, Hiroshi Nakajima, Kotaro Kumano, S. Kubo, Hajime Karasuyama, Itsuo IwamotoAbstract:Recent studies with gene knockout mice have demonstrated that T helper 2 (Th2) Cell-derived cytokines, including IL-4, IL-5, and IL-13, play important roles in causing allergic airway inflammation. In addition to Th2 cytokines, IgE-dependent activation of mast Cells has been suggested to play a role in allergic airway inflammation. In this review, we will discuss the role of IgE in Th2 Cell-mediated allergic airway inflammation. We used IgE transgenic mice, which enabled us to investigate the role of IgE without the influence of activated T Cells and other immunoglobulins. Whereas IgE cross-linking by antigens did not induce eosinophil recruitment into the airways or airway hyperreactivity, IgE cross-linking induced CD4+ T Cell recruitment into the airways. In addition, when antigen-specific Th2 Cells were transferred to IgE transgenic mice, IgE cross-linking significantly enhanced antigen-induced eosinophil recruitment into the airways. These findings suggest that IgE-dependent mast Cell activation plays an important role in allergic airway inflammation by recruiting Th2 Cells into the site of allergic inflammation.
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Stat5a regulates T helper Cell differentiation by several distinct mechanisms
Blood, 2001Co-Authors: Shin-ichiro Kagami, Akira Suto, Sumiyo Morita, Ikunoshin Kato, Yasushi Saito, Toshio Kitamura, Kotaro Suzuki, Koichi Hirose, Hiroshi Nakajima, Itsuo IwamotoAbstract:We have previously shown that CD4+ T Cell–mediated allergic inflammation is diminished in signal transducer and activator of transcription (Stat)5a-deficient (Stat5a−/−) mice. To determine whether Stat5a regulates T helper Cell differentiation, we studied T helper (Th)1 and Th2 Cell differentiation of Stat5a−/−CD4+ T Cells at single-Cell levels. First, Th2 Cell differentiation from antigen-stimulated splenocytes was significantly decreased in Stat5a−/− mice as compared with that in wild-type mice. Further, Th2 Cell differentiation was also impaired in Stat5a−/− mice even when purified CD4+ T Cells were stimulated with anti-CD3 plus anti-CD28 antibodies in the presence of interleukin-4. Moreover, the retrovirus-mediated gene expression of Stat5a in Stat5a−/−CD4+ T Cells restored the Th2 Cell differentiation at the similar levels to that in wild-type CD4+ T Cells. In addition, interleukin-4 normally phosphorylated Stat6 in CD4+ T Cells from Stat5a−/− mice. Second, the development of CD4+CD25+ immunoregulatory T Cells was impaired in Stat5a−/− mice, as indicated by a significant decrease in the number of CD4+CD25+ T Cells in Stat5a−/− mice. Furthermore, the depletion of CD4+CD25+ T Cells from wild-type splenocytes significantly decreased Th2 Cell differentiation but increased Th1 Cell differentiation, whereas the depletion of CD4+CD25+ T Cells from Stat5a−/−splenocytes had no significant effect on the Th1 and Th2 Cell differentiation. Together, these results indicate that the intrinsic expression of Stat5a in CD4+ T Cells is required for Th2 Cell differentiation and that Stat5a is involved in the development of CD4+CD25+ immunoregulatory T Cells that modulate T helper Cell differentiation toward Th2 Cells.
Timotheus Y.f. Halim - One of the best experts on this subject based on the ideXlab platform.
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Group 2 innate lymphoid Cells collaborate with dendritic Cells to potentiate memory Th2 Cell responses.
Journal of Immunology, 2016Co-Authors: Timotheus Y.f. Halim, You Yi Hwang, Seth T. Scanlon, Habib Zaghouani, Natalio Garbi, Padraic G. Fallon, Andrew N. J. MckenzieAbstract:Rapid memory CD4+ T helper 2 (Th2) Cell activation during allergic inflammation requires their recruitment into the affected tissue. Tissue-resident innate immune Cells such as dendritic Cells (DC) are essential for orchestrating local memory Th2 Cell responses. We now know that tissue-resident group 2 innate lymphoid Cells (ILC2) are an important innate source of type-2 cytokines in barrier sites. However, it is currently not known if ILC2 remain functionally important after the generation of adaptive Th2 Cells. Here we demonstrate that group 2 innate lymphoid Cells (ILC2) play a critical role in memory Th2 Cell responses. By targeted ILC2 depletion, using ILC2-specific diphtheria toxin receptor expressing iCOS-T mice, we show a profound impairment in Th2 Cell localization to the lungs and skin of sensitized mice after allergen re-challenge. Mechanistically, ILC2-derived IL-13 is critical for eliciting IRF4+CD11b+CD103− DCs to produce the Th2 Cell-attracting chemokine CCL17. Consequently, the sentinel function of DCs is contingent on ILC2s for the generation of an efficient memory Th2 Cell response. These results elucidate a key new innate mechanism in the regulation of the adaptive memory immune response to allergens.
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Group 2 innate lymphoid Cells license dendritic Cells to potentiate memory Th2 Cell responses
Nature immunology, 2015Co-Authors: Timotheus Y.f. Halim, You Yi Hwang, Seth T. Scanlon, Habib Zaghouani, Natalio Garbi, Padraic G. Fallon, Andrew N. J. MckenzieAbstract:Rapid activation of memory CD4(+) T helper 2 (Th2) Cells during allergic inflammation requires their recruitment into the affected tissue. Here we demonstrate that group 2 innate lymphoid (ILC2) Cells have a crucial role in memory Th2 Cell responses, with targeted depletion of ILC2 Cells profoundly impairing Th2 Cell localization to the lungs and skin of sensitized mice after allergen re-challenge. ILC2-derived interleukin 13 (IL-13) is critical for eliciting production of the Th2 Cell-attracting chemokine CCL17 by IRF4(+)CD11b(+)CD103(-) dendritic Cells (DCs). Consequently, the sentinel function of DCs is contingent on ILC2 Cells for the generation of an efficient memory Th2 Cell response. These results elucidate a key innate mechanism in the regulation of the immune memory response to allergens.
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group 2 innate lymphoid Cells are critical for the initiation of adaptive t helper 2 Cell mediated allergic lung inflammation
Immunity, 2014Co-Authors: Timotheus Y.f. Halim, Andrew N. J. Mckenzie, Catherine A Steer, Laura Matha, Matthew J Gold, Itziar Martinezgonzalez, Kelly M Mcnagny, Fumio TakeiAbstract:Naive CD4+ T Cell differentiation into distinct subsets of T helper (Th) Cells is a pivotal process in the initiation of the adaptive immune response. Allergens predominantly stimulate Th2 Cells, causing allergic inflammation. However, why allergens induce Th2 Cell differentiation is not well understood. Here we show that group 2 innate lymphoid Cells (ILC2s) are required to mount a robust Th2 Cell response to the protease-allergen papain. Intranasal administration of papain stimulated ILC2s and Th2 Cells, causing allergic lung inflammation and elevated immunoglobulin E titers. This process was severely impaired in ILC2-deficient mice. Whereas interleukin-4 (IL-4) was dispensable for papain-induced Th2 Cell differentiation, ILC2-derived IL-13 was critical as it promoted migration of activated lung dendritic Cells into the draining lymph node where they primed naive T Cells to differentiate into Th2 Cells. Papain-induced ILC2 activation and Th2 Cell differentiation was IL-33-dependent, suggesting a common pathway in the initiation of Th2 Cell responses to allergen.
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lung natural helper Cells are a critical source of Th2 Cell type cytokines in protease allergen induced airway inflammation
Immunity, 2012Co-Authors: Timotheus Y.f. Halim, Ramona H Kraus, Fumio TakeiAbstract:Summary Overproduction of cytokines by T helper 2 (Th2) Cells in the lung is thought to be a cause of asthma. Here we report that innate lymphocytes termed lung natural helper (LNH) Cells are a T Cell-independent source of Th2 Cell-type cytokines in protease allergen-treated lungs. LNH (Lin − Sca-1 + c-kit +/lo CD25 + CD127 + ) Cells, when stimulated by IL-33 plus IL-2, IL-7, or thymic stroma lymphopoietin (TSLP), produced large amounts of IL-5 and IL-13. Intranasal administration of protease allergen papain induced eosinophil infiltration and mucus hyperproduction in the lung of wild-type and Rag1 −/− mice, but not in Rag2 −/− Il2rg −/− mice that lack LNH Cells. LNH Cell depletion inhibited papain-induced airway inflammation in Rag1 −/− mice whereas adoptive transfer of LNH Cells enabled Rag2 −/− Il2rg −/− mice to respond to papain. Treatment of lung explants with papain induced IL-33 and TSLP production by stroma Cells and IL-5 and IL-13 production by LNH Cells. Thus, LNH Cells are critical for protease allergen-induced airway inflammation.
Foo Y Liew - One of the best experts on this subject based on the ideXlab platform.
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type 2 innate lymphoid Cells drive cd4 Th2 Cell responses
Journal of Immunology, 2014Co-Authors: Ananda S Mirchandani, Annegaelle Besnard, Edwin Yip, Charlotte L Scott, Calum C Bain, Vuk Cerovic, Robert J Salmond, Foo Y LiewAbstract:CD4+ T Cells have long been grouped into distinct helper subsets on the basis of their cytokine-secretion profile. In recent years, several subsets of innate lymphoid Cell have been described as key producers of these same Th-associated cytokines. However, the functional relationship between Th Cells and innate lymphoid Cells (ILCs) remains unclear. We show in this study that lineage-negative ST2+ICOS+CD45+ type 2 ILCs and CD4+ T Cells can potently stimulate each other’s function via distinct mechanisms. CD4+ T Cell provision of IL-2 stimulates type 2 cytokine production by type 2 ILCs. By contrast, type 2 ILCs modulate naive T Cell activation in a Cell contact–dependent manner, favoring Th2 while suppressing Th1 differentiation. Furthermore, a proportion of type 2 ILCs express MHC class II and can present peptide Ag in vitro. Importantly, cotransfer experiments show that type 2 ILCs also can boost CD4+ T Cell responses to Ag in vivo.
