Human thymic stromal lymphopoietin preferentially stimulates myeloid cells

The sequence of a novel hemopoietic cytokine was discovered in a computatio nal screen of genomic databases, and its homology to mouse thymic stromal l ymphopoietin (TSLP) suggests that it is the human orthologue. Human TSLP is proposed to signal through a heterodimeric receptor complex that consists of a new member of the hemopoietin family termed human TSLP receptor and th e IL-7R a-chain. Cells transfected with both receptor subunits proliferated in response to purified, recombinant human TSLP, with induced phosphorylat ion of Stat3 and Stat5. Human TSLPR and IL-7R alpha are principally coexpre ssed on monocytes and dendritic cell populations and to a much lesser exten t on various lymphoid cells. In accord, we find that human TSLP functions m ainly on myeloid cells; it induces the release of T cell-attracting chemoki nes from monocytes and, in particular, enhances the maturation of CD11c(+) dendritic cells, as evidenced by the strong induction of the costimulatory molecules CD40 and CD80 and the enhanced capacity to elicit proliferation o f naive T cells.