TGF-β Controls the Formation of Kidney-Resident T Cells via Promoting Effector T Cell Extravasation

Abstract

Tissue-resident memory T (T_RM) cells, a population of noncirculating memory T cells, are one of the essential components of immunological memory in both mouse and human. Although CD69⁺CD103⁺ T_RM cells represent a major T_RM cell population in barrier tissues including the mucosal surface and the skin, CD69⁺CD103^- T_RM cells dominate most nonbarrier tissues, such as the kidney. TGF-β is required for the differentiation of CD69⁺CD103⁺ T_RM cells in barrier tissues. However, the developmental control of CD69⁺CD103^- T_RM cells in nonbarrier tissues remains largely unknown and the involvement of TGF-β signaling is less clear. In this study we demonstrated that TGF-β promoted the formation of kidney-resident T cells via enhancing the tissue entry of effector T cells. Mechanistically, TGF-β enhanced E- and P-selectin and inflammatory chemokine-mediated extravasation of effector T cells. Thus TGF-β controls the first developmental checkpoint of T_RM cell differentiation in nonbarrier tissues.