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 (Teffs), which drive the immune response, and regulatory T cells (Tregs), which suppress the response, is required for proper immune homeostasis. Here, we report that TSLP differentially acts on Teffs versus Tregs to balance type 2 immunity. As expected, deletion of TSLP receptor (TSLPR) on all T cells (Cd4CreCrlf2fl/fl mice) resulted in lower numbers of T helper 2 (TH2) cells and diminished ovalbumin-induced airway inflammation, but selective deletion of TSLPR on Tregs (Foxp3YFP-Cre/YCrlf2fl/fl mice) resulted in increased interleukin-5 (IL-5)- and IL-13-secreting TH2 cells and lung eosinophilia. Moreover, TSLP augmented the expression of factors that stabilize Tregs. During type 2 immune responses, TSLPR-deficient Tregs acquired TH2-like properties, with augmented GATA3 expression and secretion of IL-13. TSLP not only is a driver of TH2 effector cells but also acts in a negative feedback loop, thus promoting the ability of Tregs to limit allergic inflammation.