Interleukin-15 in autoimmunity

被引：51
作者：
Allard-Chamard, Hugues [1 ,2 ]
Mishra, Hemant K. [3 ]
Nandi, Madhuparna [4 ]
Mayhue, Marian [4 ]
Menendez, Alfredo [2 ,5 ]
Ilangumaran, Subburaj [2 ,4 ]
Ramanathan, Sheela [2 ,4 ]
机构：
[1] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Med, Div Rheumatol, Sherbrooke, PQ J1H 5N4, Canada
[2] Ctr Hosp Univ Sherbrooke, Ctr Rech Clin, Sherbrooke, PQ, Canada
[3] Univ Minnesota, Vet & Biomed Sci, Minneapolis, MN USA
[4] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Immunol & Cell Biol, 3001 North 12th Ave, Sherbrooke, PQ J1H 5N4, Canada
[5] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Microbiol & Infect Dis, Sherbrooke, PQ, Canada
来源：
CYTOKINE | 2020年 / 136卷
基金：
加拿大自然科学与工程研究理事会;
关键词：
IL-15; Autoimmunity; Rheumatoid arthritis; Type; 1; diabetes; Immunotherapy; TUMOR-NECROSIS-FACTOR; CD8; T-CELLS; INNATE LYMPHOID-CELLS; NATURAL-KILLER-CELLS; SUPERAGONIST COMPLEX ALT-803; MESSENGER-RNA ISOFORMS; RECEPTOR ALPHA-CHAIN; RHEUMATOID-ARTHRITIS; IL-15; RECEPTOR; TRANS-PRESENTATION;
D O I：
10.1016/j.cyto.2020.155258
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Interleukin-15 (IL-15) is a member of the IL-2 family of cytokines, which use receptor complexes containing the common gamma (gamma(c)) chain for signaling. IL-15 plays important roles in innate and adaptative immune responses and is implicated in the pathogenesis of several immune diseases. The IL-15 receptor consists of 3 subunits namely, the ligand-binding IL-15R alpha chain, the beta chain (also used by IL-2) and the gamma(c) chain. IL-15 uses a unique signaling pathway whereby IL-15 associates with IL-15R alpha during biosynthesis, and this complex is 'trans-presented' to responder cells that expresses the IL-2/15R beta gamma(c) receptor complex. IL-15 is subject to post-transcriptional and post-translational regulation, and evidence also suggests that IL-15 cis-signaling can occur under certain conditions. IL-15 has been implicated in the pathology of various autoimmune diseases such as rheumatoid arthritis, autoimmune diabetes, inflammatory bowel disease, coeliac disease and psoriasis. Studies with pre-clinical models have shown the beneficial effects of targeting IL-15 signaling in autoimmunity. Unlike therapies targeting other cytokines, anti-IL-15 therapies have not yet been successful in humans. We discuss the complexities of IL-15 signaling in autoimmunity and explore potential immunotherapeutic approaches to target the IL-15 signaling pathway.
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页数：15
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