title: Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells.
abstract: Compelling evidence suggests that the epithelial cell-derived cytokine thymic stromal lymphopoietin (TSLP) may initiate asthma or atopic dermatitis through a dendritic cell-mediated T helper (Th)2 response. Here, we describe how TSLP might initiate and aggravate allergic inflammation in the absence of T lymphocytes and immunoglobulin E antibodies via the innate immune system. We show that TSLP, synergistically with interleukin 1 and tumor necrosis factor, stimulates the production of high levels of Th2 cytokines by human mast cells (MCs). We next report that TSLP is released by primary epithelial cells in response to certain microbial products, physical injury, or inflammatory cytokines. Direct epithelial cell-mediated, TSLP-dependent activation of MCs may play a central role in "intrinsic" forms of atopic diseases and explain the aggravating role of infection and scratching in these diseases.
authors.affiliation: Laboratory on Allergy, CHUM Research Center, Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada.
authors.forename: Zoulfia
authors.initials: Z
authors.lastname: Allakhverdi
authors.forename: Michael R
authors.initials: MR
authors.lastname: Comeau
authors.forename: Heidi K
authors.initials: HK
authors.lastname: Jessup
authors.forename: Bo-Rin Park
authors.initials: BR
authors.lastname: Yoon
authors.forename: Avery
authors.initials: A
authors.lastname: Brewer
authors.forename: Suzanne
authors.initials: S
authors.lastname: Chartier
authors.forename: Nicole
authors.initials: N
authors.lastname: Paquette
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
authors.forename: Marika
authors.initials: M
authors.lastname: Sarfati
authors.forename: Guy
authors.initials: G
authors.lastname: Delespesse
mesh_terms: D000704:Analysis of Variance; D016207:Cytokines / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology*; D007113:Immunity, Innate / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D016133:Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: C498762:CRLF2 protein, human; D016207:Cytokines; D018076:DNA, Complementary; D018121:Receptors, Cytokine; D000094632:Thymic Stromal Lymphopoietin