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The Journal of Immunology, 2001, 167: 336-343.
Copyright © 2001 by The American Association of Immunologists

Human Thymic Stromal Lymphopoietin Preferentially Stimulates Myeloid Cells1

Pedro A. Reche, Vassili Soumelis, Daniel M. Gorman, Teresa Clifford, Man-ru Liu, Marilyn Travis, Sandra M. Zurawski, Jim Johnston, Yong-Jun Liu, Hergen Spits, Rene de Waal Malefyt, Robert A. Kastelein2 and J. Fernando Bazan

DNAX Research Institute, Palo Alto, CA 94304

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-7R{alpha} 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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