TSLP acts on regulatory T cells to maintain their identity and limit allergic inflammation

Thymic stromal lymphopoietin (TSLP) is a type I cytokine that promotes allergic responses and mediates type 2 immunity. A balance between effector T cells (T_effs), which drive the immune response, and regulatory T cells (T_regs), which suppress the response, is required for proper immune homeostasis. Here, we report that TSLP differentially acts on T_effs versus T_regs to balance type 2 immunity. As expected, deletion of TSLP receptor (TSLPR) on all T cells (Cd4^CreCrlf2^fl/fl mice) resulted in lower numbers of T helper 2 (T_H2) cells and diminished ovalbumin-induced airway inflammation, but selective deletion of TSLPR on T_regs (Foxp3Crlf2^fl/fl mice) resulted in increased interleukin-5 (IL-5)- and IL-13-secreting T_H2 cells and lung eosinophilia. Moreover, TSLP augmented the expression of factors that stabilize T_regs. During type 2 immune responses, TSLPR-deficient T_regs acquired T_H2-like properties, with augmented GATA3 expression and secretion of IL-13. TSLP not only is a driver of T_H2 effector cells but also acts in a negative feedback loop, thus promoting the ability of T_regs to limit allergic inflammation.