上皮内淋巴细胞
T细胞受体
免疫学
髓样
生物
肠上皮
上皮
淋巴细胞
T细胞
细胞生物学
癌症研究
免疫系统
遗传学
作者
Sarah Mann Danielson,Adam R. Lefferts,Eric Norman,Emilie Regner,Hanna M. Schulz,Danielle Sansone-Poe,David J. Orlicky,Kristine A. Kuhn
标识
DOI:10.4049/jimmunol.2200556
摘要
Intraepithelial lymphocytes (IELs) are T cells important for the maintenance of barrier integrity in the intestine. Colon IELs are significantly reduced in both MyD88-deficient mice and those lacking an intact microbiota, suggesting that MyD88-mediated detection of bacterial products is important for the recruitment and/or retention of these cells. Here, using conditionally deficient MyD88 mice, we show that myeloid cells are the key mediators of TCRαβ+ IEL recruitment to the colon. Upon exposure to luminal bacteria, myeloid cells produce sphingosine-1-phosphate (S1P) in a MyD88-dependent fashion. TCRαβ+ IEL recruitment may be blocked using the S1P receptor antagonist FTY720, confirming the importance of S1P in the recruitment of TCRαβ+ IELs to the colon epithelium. Finally, using the TNFΔARE/+ model of Crohn's-like bowel inflammation, we show that disruption of colon IEL recruitment through myeloid-specific MyD88 deficiency results in reduced pathology. Our results illustrate one mechanism for recruitment of a subset of IELs to the colon.
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