γδ T Cells Coexpressing Gut Homing α4β7 and αE Integrins Define a Novel Subset Promoting Intestinal Inflammation.
γδ T Cells Coexpressing Gut Homing α4β7 and αE Integrins Define a Novel Subset Promoting Intestinal Inflammation.
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DOI：
10.4049/jimmunol.1601060
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发表时间：
2017-01-15
期刊：
影响因子：
--
通讯作者：
Min B
中科院分区：
文献类型：
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作者：
Do JS;Kim S;Keslar K;Jang E;Huang E;Fairchild RL;Pizarro TT;Min B
γδ T淋巴细胞是肠道中的主要T细胞亚群，介导调节和致病作用，但这种相反作用的机制仍不清楚。在这里，我们鉴定了一种独特的γδ T细胞亚群，其共表达高水平的肠道归巢整合素CD 103和α4β7。它们仅在T细胞介导的结肠炎诱导后的mLN中发现，并且它们的出现在炎症之前。CD 103 +α4β 7 high亚群的连续转移促进了Th 1/Th 17 T细胞在肠道内的生成和积聚，并加重了疾病的严重程度。世代水平与病情严重程度相关。此外，还发现这些细胞在自发性回肠炎小鼠模型中升高。基于促结肠炎功能，我们将该亚群称为“炎性”γδ（iγδ）T细胞。靶向γδ T细胞可能开辟了一种治疗炎性疾病的新策略，其中γδ T细胞发挥致病作用，包括炎性肠病。
γδ T lymphocytes, dominant T cell subsets in the intestine, mediate both regulatory and pathogenic roles, yet the mechanisms underlying such opposing effects remain unclear. Here, we identified a unique γδ T cell subset that co-expresses high levels of gut homing integrins, CD103 and α4β7. They were exclusively found in the mLN following T cell-mediated colitis induction and their appearance preceded the inflammation. Adoptive transfer of the CD103+α4β7high subsets enhanced Th1/Th17 T cell generation and accumulation in the intestine, and the disease severity. The level of generation correlated with the disease severity. Moreover, these cells were also found to be elevated in a spontaneous mouse model of ileitis. Based on the pro-colitogenic function, we referred to this subset as ‘inflammatory’ γδ (iγδ) T cells. Targeting iγδ T cells may open a novel strategy to treat inflammatory diseases where γδ T cells play a pathogenic role including inflammatory bowel disease.