Human thymic stromal lymphopoietin preferentially stimulates myeloid cells.
Reche PA,
Soumelis V,
Gorman DM,
Clifford T,
Liu Mr,
Travis M,
Zurawski SM,
Johnston J,
Liu YJ,
Spits H,
de Waal Malefyt R,
Kastelein RA,
Bazan JF.
DNAX Research Institute, Palo Alto, CA 94304, USA.
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.
PMID: 11418668 [PubMed - indexed for MEDLINE]