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

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-gamma, 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.