| IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. | |
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MedLine Citation:
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PMID: 22324470 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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IL-17 (interleukin-17), a hallmark cytokine of Th17 (T-helper 17) cells, plays critical roles in host defence against bacterial and fungal infections, as well as in the pathogenesis of autoimmune diseases. The present review focuses on current knowledge of the regulation, functional mechanisms and targeting strategies of IL-17 in the context of inflammatory autoimmune diseases. Evidence shows that IL-17 is highly up-regulated at sites of inflammatory tissues of autoimmune diseases and amplifies the inflammation through synergy with other cytokines, such as TNF (tumour necrosis factor) α. Although IL-17 was originally thought to be produced mainly by Th17 cells, a newly defined T-cell subset with a specific differentiation programme and tight regulation, several other cell types (especially innate immune cells) are also found as important sources for IL-17 production. Although IL-17 activates common downstream signalling, including NF-κB (nuclear factor κB), MAPKs (mitogen-activated protein kinases), C/EBPs (CCAAT/enhancer-binding proteins) and mRNA stability, the immediate receptor signalling has been shown to be quite unique and tightly regulated. Mouse genetic studies have demonstrated a critical role for IL-17 in the pathogenesis of variety of inflammatory autoimmune diseases, such as RA (rheumatoid arthritis) and MS (multiple sclerosis). Importantly, promising results have been shown in initial clinical trials of monoclonal antibodies against IL-17 or its receptor (IL-17R) to block IL-17-mediated function in treating autoimmune patients with psoriasis, RA and MS. Therefore targeting IL-17/IL-17R, IL-17-producing pathways or IL-17-mediated signalling pathways can be considered for future therapy in autoimmune diseases. |
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Authors:
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Shu Zhu; Youcun Qian |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Clinical science (London, England : 1979) Volume: 122 ISSN: 1470-8736 ISO Abbreviation: Clin. Sci. Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-02-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7905731 Medline TA: Clin Sci (Lond) Country: England |
Other Details:
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Languages: eng Pagination: 487-511 Citation Subset: IM |
Affiliation:
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The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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