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 Cre Crlf2 fl/fl mice) resulted in lower numbers of T helper 2 (T H 2) cells and diminished ovalbumin-induced airway inflammation, but selective deletion of TSLPR on T regs ( Foxp3 YFP -Cre/Y Crlf2 fl/fl mice) resulted in increased interleukin-5 (IL-5)– and IL-13–secreting T H 2 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 H 2-like properties, with augmented GATA3 expression and secretion of IL-13. TSLP not only is a driver of T H 2 effector cells but also acts in a negative feedback loop, thus promoting the ability of T regs to limit allergic inflammation.