Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake

Abstract

Epithelial cells control a variety of immune cells by secreting cytokines to maintain tissue homeostasis on mucosal surfaces. Regulatory T (Treg) cells are essential for immune homeostasis and for preventing tissue inflammation; however, the precise molecular mechanisms by which epithelial cell-derived cytokines function on Treg cells in the epithelial tissues are not well understood. Here, we show that peripheral Treg cells preferentially respond to thymic stromal lymphoprotein (TSLP). Although TSLP does not affect thymic Treg differentiation, TSLP receptor-deficient induced Treg cells derived from naïve CD4+ T cells are less activated in an adoptive transfer model of colitis. Mechanistically, TSLP activates induced Treg cells partially through mTORC1 activation and fatty acid uptake. Thus, TSLP modulates the activation status of induced Treg through the enhanced uptake of fatty acids to maintain homeostasis in the large intestine.

Type III interferon exerts thymic stromal lymphopoietin in mediating adaptive antiviral immune response

“…Later, TSLP-dependent germinal center (GC) B cells in lymph nodes are activated and thus numerous high-affinity IgA and IgG antibodies are secreted ( 33 , 90 ). Besides, apart from the critical role of IFN-III in mucosal homeostasis ( 91 ), TSLP has also been found highly expressed in antigen-stimulated colonic epithelial cells, which in turn activates Tregs through the mTORC1 pathway to maintain mucosal homeostasis ( 92 ). Hence, the IFN-III/TSLP axis may also participate in modulating mucosal homeostasis to some extent ( Figure 2 , left).…”