Targeting Th17 cells in autoimmune diseases

被引：427

作者：

Yang, Jianfei ^{[1
]}

Sundrud, Mark S. ^{[2
]}

Skepner, Jill ^{[1
]}

Yamagata, Tetsuya ^{[1
]}

机构：

[1] Tempero Pharmaceut, Cambridge, MA 02139 USA

[2] Scripps Res Inst, Dept Canc Biol, Jupiter, FL 33458 USA

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2014年 / 35卷 / 10期

关键词：

IL-17; IL-23; ROR gamma t; autoimmune diseases; INTERLEUKIN-12/23; MONOCLONAL-ANTIBODY; DOUBLE-BLIND; INDUCED ARTHRITIS; T(H)17 CELLS; T-CELLS; CARTILAGE DESTRUCTION; PHASE-II; TGF-BETA; RECEPTOR; GAMMA;

D O I：

10.1016/j.tips.2014.07.006

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

T helper 17 (Th17) cells have been implicated in the pathogenesis of most common autoimmune diseases, including psoriasis, rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and multiple sclerosis (MS). Although anti-interleukin-17 (IL-17) antibodies show marked clinical efficacy in psoriasis, targeting IL-17 alone is not sufficient to improve clinical end points in other autoimmune conditions, namely RA and Crohn's disease. Given that Th17 cells express IL-17 together with many other proinflammatory cytokines [IL-17F, IL-22, IL-26, and granulocyte-macrophage colony-stimulating factor (GM-CSF)], targeting the Th17 cell lineage may be superior to blocking a single effector cytokine. Here, we discuss the rationale for targeting two checkpoints in the development and inflammatory function of Th17 cells, retinoid-related orphan receptor-gamma t (ROR gamma t) and IL-23, and we review recent progress in the development of both ROR gamma t small molecule inhibitors and IL-23 neutralizing antibodies.

引用

页码：493 / 500

页数：8

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