上皮内淋巴细胞
生物
细胞生物学
CD8型
细胞毒性T细胞
CCL25型
趋化因子受体
细胞分化
免疫学
趋化因子
抗原
免疫系统
遗传学
基因
体外
作者
Can Li,Hye Kyung Kim,Praveen Prakhar,Shunqun Luo,Assiatu Crossman,Davinna L. Ligons,Megan A. Luckey,Parirokh Awasthi,Ronald E. Gress,Jung‐Hyun Park
标识
DOI:10.1038/s41385-022-00540-9
摘要
The chemokine receptor CCR9 equips T cells with the ability to respond to CCL25, a chemokine that is highly expressed in the thymus and the small intestine (SI). Notably, CCR9 is mostly expressed on CD8 but not on CD4 lineage T cells, thus imposing distinct tissue tropism on CD4 and CD8 T cells. The molecular basis and the consequences for such a dichotomy, however, have not been fully examined and explained. Here, we demonstrate that the forced expression of CCR9 interferes with the tissue trafficking and differentiation of CD4 T cells in SI intraepithelial tissues. While CCR9 overexpression did not alter CD4 T cell generation in the thymus, the forced expression of CCR9 was detrimental for the proper tissue distribution of CD4 T cells in the periphery, and strikingly also for their terminal differentiation in the gut epithelium. Specifically, the differentiation of SI epithelial CD4 T cells into immunoregulatory CD4+CD8αα+ T cells was impaired by overexpression of CCR9 and conversely increased by the genetic deletion of CCR9. Collectively, our results reveal a previously unappreciated role for CCR9 in the tissue homeostasis and effector function of CD4 T cells in the gut.
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