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Reche, Pedro A; Soumelis, Vassili; Gorman, Daniel M; Clifford, Teresa; Liu, Man-ru; Travis, Marilyn; Zurawski, Sandra M; Johnston, Jim; Liu, Yong-Jun; Spits, Hergen; de Waal Malefyt, Rene; Kastelein, Robert A; Bazan, J. Fernando
The Journal of immunology (1950), 07/2001, Volume: 167, Issue: 1Journal Article
The sequence of a novel hemopoietic cytokine was discovered in a computational screen of genomic databases, and its homology to mouse thymic stromal lymphopoietin (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 the IL-7R alpha-chain. Cells transfected with both receptor subunits proliferated in response to purified, recombinant human TSLP, with induced phosphorylation of Stat3 and Stat5. Human TSLPR and IL-7Ralpha are principally coexpressed on monocytes and dendritic cell populations and to a much lesser extent on various lymphoid cells. In accord, we find that human TSLP functions mainly on myeloid cells; it induces the release of T cell-attracting chemokines 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 of naive T cells.
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