Cutting edge: The ST2 ligand IL-33 potently activates and drives maturation of human mast cells.
IL-33, the natural ligand of the IL-1 receptor family member ST2L, is known to enhance experimental allergic-type inflammatory responses by costimulating the production of cytokines from activated Th2 lymphocytes. Although ST2L has long been known to be expressed by mast cells, its role in their biology has not been explored. In this study we report that IL-33 directly stimulates primary human mast cells (MCs) to produce several proinflammatory cytokines and chemokines and also exerts a permissive effect on the MCs response to thymic stromal lymphopoietin, a recently described potent MCs activator. IL-33 also acts both alone and in concert with thymic stromal lymphopoietin to accelerate the in vitro maturation of CD34(+) MC precursors and induce the secretion of Th2 cytokines and Th2-attracting chemokines. Taken together, these results suggest that IL-33 may play an important role in mast cell-mediated inflammation and further emphasize the role of innate immunity in allergic diseases.
Laboratory on Allergy, Centre Hospitalier de l'Université de Montréal Research Center, Notre-Dame Hospital, Montreal, Quebec, Canada.
Zoulfia
Z
Allakhverdi
Dirk E
DE
Smith
Michael R
MR
Comeau
Guy
G
Delespesse
D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D018925:Chemokines; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D011956:Receptors, Cell Surface