The Experts below are selected from a list of 109236 Experts worldwide ranked by ideXlab platform
Chen Dong - One of the best experts on this subject based on the ideXlab platform.
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IL-17C is required for lethal inflammation during systemic fungal infection.
Cellular & molecular immunology, 2015Co-Authors: Jinling Huang, Shaoshuai Meng, Shanjuan Hong, Xin Lin, Wei Jin, Chen DongAbstract:Within the interleukin-17 (IL-17) famILy of cytokines, IL-17A is known to be critical in the host defense against fungal infections; however, the function of the other IL-17 famILy members in anti-fungal immunity remains largely unknown. Here, we show that IL-17C expression was highly induced in kidney epithelial cells after fungal infection. Mice that lacked IL-17C exhibited increased survival and attenuated kidney tissue damage, although they had simILar fungal loads. IL-17C deficiency resulted in decreased pro-inflammatory cytokine expression compared with wILd-type control mice. Additionally, IL-17C directly acted on renal epithelial cells in vitro to promote pro-inflammatory cytokine production. Taken together, our data demonstrate that IL-17C is a critical factor that potentiates inflammatory responses and causes host injury during fungal infection.
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Interleukin-17B Antagonizes Interleukin-25-Mediated Mucosal Inflammation.
Immunity, 2015Co-Authors: Joseph M. Reynolds, Pornpimon Angkasekwinai, Young Hee Lee, Yun Shi, Xiaohu Wang, Kalyan C. Nallaparaju, Stephanie Flaherty, Seon Hee Chang, Hiroshi Watarai, Chen DongAbstract:The interleukin-17 (IL-17) famILy of cytokines has emerged as a critical player in inflammatory diseases. Among them, IL-25 has been shown to be important in allergic inflammation and protection against parasitic infection. Here we have demonstrated that IL-17B, a poorly understood cytokine, functions to inhibit IL-25-driven inflammation. IL-17B and IL-25, both binding to the interleukin-17 receptor B (IL-17RB), were upregulated in their expression after acute colonic inflammation. Individual inhibition of these cytokines revealed opposing functions in colon inflammation: IL-25 was pathogenic but IL-17B was protective. SimILarly opposing phenotypes were observed in Citrobacter rodentium infection and allergic asthma. Moreover, IL-25 was found to promote IL-6 production from colon epithelial cells, which was inhibited by IL-17B. Therefore, our data demonstrate that IL-17B is an anti-inflammatory cytokine in the IL-17 famILy.
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Signaling of interleukin-17 famILy cytokines in immunity and inflammation.
Cellular signalling, 2010Co-Authors: Seon Hee Chang, Chen DongAbstract:IL-17 cytokine famILy, though stILl young since discovery, has recently emerged as critical players in immunity and inflammatory diseases. The prototype cytokine, IL-17A, plays essential roles in promoting inflammation and host defense. IL-17RA, a member of the IL-17 receptor famILy, forms a complex with another member, IL-17RC, to mediate effective signaling for IL-17A as well as IL-17F, which is most simILar to IL-17A, via Act1 and TRAF6 factors. On the other hand, IL-17RA appears to interact with IL-17RB to regulate signaling by another cytokine IL-25. IL-25, the most distant from IL-17A in the IL-17 famILy, is involved in allergic disease and defense against helminthic parasites. In this review, we discuss recent advancements on signaling mechanisms and biological functions of IL-17A, IL-17F and IL-25, which wILl shed light on the remaining IL-17 famILy cytokines and help understand and treat inflammatory diseases.
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IL-17 famILy member cytokines: regulation and function in innate immunity.
Cytokine & growth factor reviews, 2010Co-Authors: Joseph M. Reynolds, Pornpimon Angkasekwinai, Chen DongAbstract:Recently, the IL-17 famILy member cytokines have become prominent subjects of investigation. IL-17 (IL-17A) is the best-described member of this famILy where its production has been mainly attributed to a specialized T helper subset of the adaptive immune response termed Th17. However, recent research on this and other Th17 cytokines has revealed new sources and functions of IL-17 famILy members in the innate immune response. This review wILl highlight recent advances in the field of IL-17 famILy member cytokines and wILl predominately focus on the innate regulation and function of IL-17, IL-17F, and IL-25.
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Regulatory mechanisms of helper T cell differentiation: new lessons learned from interleukin 17 famILy cytokines.
Pharmacology & therapeutics, 2008Co-Authors: Bhanu P. Pappu, Pornpimon Angkasekwinai, Chen DongAbstract:Interleukin 17 (IL-17) famILy consists of six cytokines in mammals. Among them, IL-17 and IL-17F are expressed by a novel subset of CD4+ helper T (Th) cells and play critical function in inflammation and autoimmunity. On the other hand, IL-17E, also called IL-25, has been associated with allergic responses. Here we summarize recent work by us as well as other investigators in understanding the regulation and function of these three cytokines. From these studies, IL-17 famILy cytokines may serve as novel targets for pharmaceutical intervention of immune and inflammatory diseases.
Estefania Claudio - One of the best experts on this subject based on the ideXlab platform.
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Critical target cell-specific roles for IL-17 famILy cytokines/CIKS-mediated signaling in mouse models of skin and lung inflammation (CCR6P.276)
Journal of Immunology, 2014Co-Authors: Ulrich Siebenlist, Estefania ClaudioAbstract:The inflammatory cytokine IL-17 has been strongly implicated in human psoriasis and in the imiquimod-induced mouse model of this disease, whILe the IL-17 famILy member IL-25 has been associated with allergic asthma in humans and with allergen-induced inflammation in mouse models. Both cytokines signal via the obligatory adaptor protein CIKS (a.k.a. Act1 or Traf3ip2). However what cells are targeted by these cytokines and to what end has not been clearly delineated in these disease contexts. We demonstrate that in imiquimod-induced psoriatic inflammation, IL-17 signals into keratinocytes to dysregulate their growth/differentiation. On the other hand, IL-17 signals into non-keratinocytes to promote cellular infILtration in this psoriasis model and to drive a positive feedback loop, resulting in increased production of IL-17. We further demonstrate that in a chronic house dust mite-induced asthma model, IL-25 uniquely contributes to generation of Th9 cells and to airway remodeling, at least in part by targeting dendritic-like cells. These findings reveal previously unappreciated, cell-type specific functions IL-17 cytokines that contribute to inflammatory diseases at barrier sites.
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critical target cell specific roles for IL 17 famILy cytokines ciks mediated signaling in mouse models of skin and lung inflammation ccr6p 276
Journal of Immunology, 2014Co-Authors: Ulrich Siebenlist, Estefania ClaudioAbstract:The inflammatory cytokine IL-17 has been strongly implicated in human psoriasis and in the imiquimod-induced mouse model of this disease, whILe the IL-17 famILy member IL-25 has been associated with allergic asthma in humans and with allergen-induced inflammation in mouse models. Both cytokines signal via the obligatory adaptor protein CIKS (a.k.a. Act1 or Traf3ip2). However what cells are targeted by these cytokines and to what end has not been clearly delineated in these disease contexts. We demonstrate that in imiquimod-induced psoriatic inflammation, IL-17 signals into keratinocytes to dysregulate their growth/differentiation. On the other hand, IL-17 signals into non-keratinocytes to promote cellular infILtration in this psoriasis model and to drive a positive feedback loop, resulting in increased production of IL-17. We further demonstrate that in a chronic house dust mite-induced asthma model, IL-25 uniquely contributes to generation of Th9 cells and to airway remodeling, at least in part by targeting dendritic-like cells. These findings reveal previously unappreciated, cell-type specific functions IL-17 cytokines that contribute to inflammatory diseases at barrier sites.
Ulrich Siebenlist - One of the best experts on this subject based on the ideXlab platform.
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Differential requirements of IL-17 famILy cytokines in host defense against oral candidiasis (CCR6P.272)
Journal of Immunology, 2014Co-Authors: Natasha Whibley, Anna J. Mamo, Heather R. Conti, Elisabetta Traggiai, Frank Kolbinger, Beate Vogel, Michael Kammueller, Ulrich Siebenlist, Yoichiro Iwakura, Sarah L. GaffenAbstract:Antibodies against IL-17A and IL-17RA are in clinical trials for autoimmunity. Mutations in IL-17 signaling genes (IL17RA, IL17F, ACT1) cause susceptibILity to mucocutaneous infection by the fungus Candida albicans. IL-17A, IL-17F and IL-17C all signal via IL-17RA, but their individual roles in controlling candidiasis are poorly defined. Accordingly, in vivo Ab neutralization of cytokines or knockout mice were evaluated in a model of oropharyngeal candidiasis (OPC). Following C. albicans exposure, tongue fungal burden after 4 d, weight change and target gene expression were assessed. Anti-IL-17A-treated mice showed modestly impaired clearance compared to WT at d4, whereas α-IL-17F-treated mice were not affected. However, IL-17RA-/- and Act1-/- mice were far more susceptible to OPC than α-IL-17A treated mice at 4 and 14 d, indicating contributions to immunity beyond IL-17A. SusceptibILity was associated with reduced expression of IL-17-regulated genes encoding chemokines and defensins. In contrast to α-IL-17A-treated mice, IL-17A-/- mice showed no significant susceptibILity to OPC. This discrepancy was not explained by contributions from IL-17F or IL-17C, because α-IL-17F-treated IL-17A-/- mice and IL-17C-/- mice cleared the infection as well as WT mice. The increased susceptibILity of IL-17RA-/- and Act1-/- mice vs. those lacking specific cytokines implies compensation between IL-17 famILy cytokines and possibly additional antifungal effectors. Funded by Novartis and NIDCR.
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Critical target cell-specific roles for IL-17 famILy cytokines/CIKS-mediated signaling in mouse models of skin and lung inflammation (CCR6P.276)
Journal of Immunology, 2014Co-Authors: Ulrich Siebenlist, Estefania ClaudioAbstract:The inflammatory cytokine IL-17 has been strongly implicated in human psoriasis and in the imiquimod-induced mouse model of this disease, whILe the IL-17 famILy member IL-25 has been associated with allergic asthma in humans and with allergen-induced inflammation in mouse models. Both cytokines signal via the obligatory adaptor protein CIKS (a.k.a. Act1 or Traf3ip2). However what cells are targeted by these cytokines and to what end has not been clearly delineated in these disease contexts. We demonstrate that in imiquimod-induced psoriatic inflammation, IL-17 signals into keratinocytes to dysregulate their growth/differentiation. On the other hand, IL-17 signals into non-keratinocytes to promote cellular infILtration in this psoriasis model and to drive a positive feedback loop, resulting in increased production of IL-17. We further demonstrate that in a chronic house dust mite-induced asthma model, IL-25 uniquely contributes to generation of Th9 cells and to airway remodeling, at least in part by targeting dendritic-like cells. These findings reveal previously unappreciated, cell-type specific functions IL-17 cytokines that contribute to inflammatory diseases at barrier sites.
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critical target cell specific roles for IL 17 famILy cytokines ciks mediated signaling in mouse models of skin and lung inflammation ccr6p 276
Journal of Immunology, 2014Co-Authors: Ulrich Siebenlist, Estefania ClaudioAbstract:The inflammatory cytokine IL-17 has been strongly implicated in human psoriasis and in the imiquimod-induced mouse model of this disease, whILe the IL-17 famILy member IL-25 has been associated with allergic asthma in humans and with allergen-induced inflammation in mouse models. Both cytokines signal via the obligatory adaptor protein CIKS (a.k.a. Act1 or Traf3ip2). However what cells are targeted by these cytokines and to what end has not been clearly delineated in these disease contexts. We demonstrate that in imiquimod-induced psoriatic inflammation, IL-17 signals into keratinocytes to dysregulate their growth/differentiation. On the other hand, IL-17 signals into non-keratinocytes to promote cellular infILtration in this psoriasis model and to drive a positive feedback loop, resulting in increased production of IL-17. We further demonstrate that in a chronic house dust mite-induced asthma model, IL-25 uniquely contributes to generation of Th9 cells and to airway remodeling, at least in part by targeting dendritic-like cells. These findings reveal previously unappreciated, cell-type specific functions IL-17 cytokines that contribute to inflammatory diseases at barrier sites.
Sarah L. Gaffen - One of the best experts on this subject based on the ideXlab platform.
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The IL-17 FamILy of Cytokines in Health and Disease.
Immunity, 2019Co-Authors: Mandy J. Mcgeachy, Daniel J. Cua, Sarah L. GaffenAbstract:The interleukin 17 (IL-17) famILy of cytokines contains 6 structurally related cytokines, IL-17A through IL-17F. IL-17A, the prototypical member of this famILy, just passed the 25th anniversary of its discovery. Although less is known about IL-17B–F, IL-17A (commonly known as IL-17) has received much attention for its pro-inflammatory role in autoimmune disease. Over the past decade, however, it has become clear that the functions of IL-17 are far more nuanced than simply turning on inflammation. Accumulating evidence indicates that IL-17 has important context- and tissue-dependent roles in maintaining health during response to injury, physiological stress, and infection. Here, we discuss the functions of the IL-17 famILy, with a focus on the balance between the pathogenic and protective roles of IL-17 in cancer and autoimmune disease, including results of therapeutic blockade and novel aspects of IL-17 signal transduction regulation.
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Interleukin 17 FamILy Cytokines: Signaling Mechanisms, Biological Activities, and Therapeutic Implications.
Cold Spring Harbor perspectives in biology, 2018Co-Authors: Leticia Monin, Sarah L. GaffenAbstract:The cytokines of the interleukin 17 (IL-17) famILy play a central role in the control of infections, especially extracellular fungi. Conversely, if unrestrained, these inflammatory cytokines contribute to the pathology of numerous autoimmune and chronic inflammatory conditions. Recent advances have led to the approval of IL-17A-blocking biologics for the treatment of moderate to severe plaque psoriasis, but much remains to be understood about the biological functions, regulation, and signaling pathways downstream of these factors. In this review, we outline the current knowledge of signal transduction and known physiological activities of IL-17 famILy cytokines. We wILl highlight in particular the current understanding of these cytokines in the context of skin manifestations of disease.
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Signaling through IL-17C/IL-17RE Is Dispensable for Immunity to Systemic, Oral and Cutaneous Candidiasis
PloS one, 2015Co-Authors: Heather R. Conti, Natasha Whibley, Bianca M. Coleman, Abhishek V. Garg, Jillian R. Jaycox, Sarah L. GaffenAbstract:Candida albicans is a commensal fungal microbe of the human orogastrointestinal tract and skin. C. albicans causes multiple forms of disease in immunocompromised patients, including oral, vaginal, dermal and disseminated candidiasis. The cytokine IL-17 (IL-17A) and its receptor subunits, IL-17RA and IL-17RC, are required for protection to most forms of candidiasis. The importance of the IL-17R pathway has been observed not only in knockout mouse models, but also in humans with rare genetic mutations that impact generation of Th17 cells or the IL-17 signaling pathway, including Hyper-IgE Syndrome (STAT3 or TYK2 mutations) or IL17RA or ACT1 gene deficiency. The IL-17 famILy of cytokines is a distinct subclass of cytokines with unique structural and signaling properties. IL-17A is the best-characterized member of the IL-17 famILy to date, but far less is known about other IL-17-related cytokines. In this study, we sought to determine the role of a related IL-17 cytokine, IL-17C, in protection against oral, dermal and disseminated forms of C. albicans infection. IL-17C signals through a heterodimeric receptor composed of the IL-17RA and IL-17RE subunits. We observed that IL-17C mRNA was induced following oral C. albicans infection. However, mice lacking IL-17C or IL-17RE cleared C. albicans infections in the oral mucosa, skin and bloodstream at rates simILar to WT littermate controls. Moreover, these mice demonstrated simILar gene transcription profILes and recovery kinetics as WT animals. These findings indicate that IL-17C and IL-17RE are dispensable for immunity to the forms of candidiasis evaluated, and ILlustrate a surprisingly limited specificity of the IL-17 famILy of cytokines with respect to systemic, oral and cutaneous Candida infections.
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Differential requirements of IL-17 famILy cytokines in host defense against oral candidiasis (CCR6P.272)
Journal of Immunology, 2014Co-Authors: Natasha Whibley, Anna J. Mamo, Heather R. Conti, Elisabetta Traggiai, Frank Kolbinger, Beate Vogel, Michael Kammueller, Ulrich Siebenlist, Yoichiro Iwakura, Sarah L. GaffenAbstract:Antibodies against IL-17A and IL-17RA are in clinical trials for autoimmunity. Mutations in IL-17 signaling genes (IL17RA, IL17F, ACT1) cause susceptibILity to mucocutaneous infection by the fungus Candida albicans. IL-17A, IL-17F and IL-17C all signal via IL-17RA, but their individual roles in controlling candidiasis are poorly defined. Accordingly, in vivo Ab neutralization of cytokines or knockout mice were evaluated in a model of oropharyngeal candidiasis (OPC). Following C. albicans exposure, tongue fungal burden after 4 d, weight change and target gene expression were assessed. Anti-IL-17A-treated mice showed modestly impaired clearance compared to WT at d4, whereas α-IL-17F-treated mice were not affected. However, IL-17RA-/- and Act1-/- mice were far more susceptible to OPC than α-IL-17A treated mice at 4 and 14 d, indicating contributions to immunity beyond IL-17A. SusceptibILity was associated with reduced expression of IL-17-regulated genes encoding chemokines and defensins. In contrast to α-IL-17A-treated mice, IL-17A-/- mice showed no significant susceptibILity to OPC. This discrepancy was not explained by contributions from IL-17F or IL-17C, because α-IL-17F-treated IL-17A-/- mice and IL-17C-/- mice cleared the infection as well as WT mice. The increased susceptibILity of IL-17RA-/- and Act1-/- mice vs. those lacking specific cytokines implies compensation between IL-17 famILy cytokines and possibly additional antifungal effectors. Funded by Novartis and NIDCR.
Nicolò Costantino Brembilla - One of the best experts on this subject based on the ideXlab platform.
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The IL-17 FamILy of Cytokines in Psoriasis: IL-17A and Beyond
Frontiers in immunology, 2018Co-Authors: Nicolò Costantino Brembilla, Luisa Senra, Wolf-henning BoehnckeAbstract:Psoriasis is a frequent chronic inflammatory skin disease, nowadays considered a major global health problem. Several new drugs, targeting the IL-23/IL-17A pathway, have been recently licensed or are in clinical development. These therapies represent a major improvement of the way in which psoriasis is managed, since they show an unprecedented efficacy on skin symptoms of psoriasis. This has been made possible, thanks to an increasingly more accurate pathogenic view of psoriasis. Today, the belief that Th17 cells mediate psoriasis is moving to the concept of psoriasis as an IL-17A-driven disease. New questions arise at the horizon, given that IL-17A is part of a newly described famILy of cytokines, which has five distinct homologous: IL-17B, IL-17C, IL-17D, IL-17E, also known as IL-25 and IL-17F. IL-17 famILy cytokines elicit simILar effects in target cells, but simultaneously trigger different and sometimes opposite functions in a tissue-specific manner. This is complicated by the fact that IL-17 cytokines show a high capacity of synergisms with other inflammatory stimuli. In this review, we wILl summarize the current knowledge around the cytokines belonging to the IL-17 famILy in relation to skin inflammation in general and psoriasis in particular, and discuss possible clinical implications. A comprehensive understanding of the different roles played by the IL-17 cytokines is crucial to appreciate current and developing therapies and to allow an effective pathogenesis- and mechanisms-driven drug design.
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High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis.
PloS one, 2014Co-Authors: Paola Adele Lonati, Nicolò Costantino Brembilla, Elisa Montanari, Lionel Fontao, Armando Gabrielli, Serena Vettori, Gabriele Valentini, Emmanuel Laffitte, Gürkan Kaya, Pier Luigi MeroniAbstract:High interleukin (IL)-17A levels are characteristically found in the skin of systemic sclerosis (SSc) individuals. Our aim was to investigate whether the dermal expression of IL-17A and related IL-17 famILy members (i.e. IL-17C, IL-17E and IL-17F) could distinguish fibrotic from healthy skin and could show simILarities in SSc and morphea, two disorders with presumed distinct pathogenesis, but characterized by skin fibrosis.
