A role for TSLP in the development of inflammation in an asthma model

Abstract

Thymic stromal lymphopoietin (TSLP) is a cytokine that promotes CD4 ⁺ T cell homeostasis. We now demonstrate that TSLP is required to mount a normal CD4 ⁺ T cell–mediated inflammatory response. TSLP acts directly on naive, but not, memory CD4 ⁺ T cells, and promotes their proliferation in response to antigen. In addition, TSLP exerts an effect indirectly through DCs to promote Th2 differentiation of CD4 ⁺ T cells. Correspondingly, TSLP receptor (TSLPR) knockout (KO) mice exhibit strong Th1 responses, with high levels of interleukin (IL)-12, interferon- γ, and immunoglobulin (Ig) G2a, but low production of IL-4, -5, -10, -13, and IgE; moreover, CD4 ⁺ T cells from these animals proliferate less well in response to antigen. Furthermore, TSLPR KO mice fail to develop an inflammatory lung response to inhaled antigen unless supplemented with wild-type CD4 ⁺ T cells. This underscores an important role for this cytokine in the development of inflammatory and/or allergic responses in vivo.