Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin

Signaling by type I cytokines involves the formation of receptor homodimers, heterodimers or higher order receptor oligomers. Here we report the cloning of a type I cytokine receptor subunit that is most closely related to the common cytokine receptor gamma chain (gamma c). Binding and crosslinking experiments demonstrate that this protein is the receptor for a recently described interleukin 7 (IL-7)-like factor, thymic stromal lymphopoietin (TSLP). Binding of TSLP to the thymic stromal lymphopoietin receptor (TSLPR) is increased markedly in the presence of the IL-7 receptor alpha chain (IL-7R alpha). IL-7R alpha-expressing but not parental 32D cells proliferate in the presence of exogenous TSLP. Moreover, a combination of IL-7R alpha and TSLPR is required for TSLP-dependent activation of a STAT5-dependent reporter construct. Thus it is shown that IL-7R alpha is a component of both the IL-7 and TSLP receptors, which helps to explain why deletion of the gene that encodes IL-7R alpha affects the lymphoid system more severely than deletion of the gene encoding IL-7 does. Cloning of TSLPR should facilitate an understanding of TSLP function and its signaling mechanism.