Human thymic stromal lymphopoietin preferentially stimulates myeloid cells.
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.
Reche
P A
PA
DNAX Research Institute, Palo Alto, CA 94304, USA.
Soumelis
V
V
Gorman
D M
DM
Clifford
T
T
Liu Mr
Travis
M
M
Zurawski
S M
SM
Johnston
J
J
Liu
Y J
YJ
Spits
H
H
de Waal Malefyt
R
R
Kastelein
R A
RA
Bazan
J F
JF
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002469:Cell Separation; D002478:Cells, Cultured; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000096:biosynthesis; D019295:Computational Biology; D016207:Cytokines / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis; D015851:Interleukin-7 / Q000378:metabolism / Q000502:physiology; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000032:analysis / Q000096:biosynthesis; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis; D017154:Stromal Cells / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*; D000094632:Thymic Stromal Lymphopoietin
C106230:CCL17 protein, human; C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; D019742:Chemokines, CC; D016207:Cytokines; D016167:Integrin alphaXbeta2; D015851:Interleukin-7; D046911:Macromolecular Substances; D018121:Receptors, Cytokine; D020395:Receptors, Interleukin-7; D000094632:Thymic Stromal Lymphopoietin