Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells.
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.
Allakhverdi
Zoulfia
Z
Laboratory on Allergy, CHUM Research Center, Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada.
Comeau
Michael R
MR
Jessup
Heidi K
HK
Yoon
Bo-Rin Park
BR
Brewer
Avery
A
Chartier
Suzanne
S
Paquette
Nicole
N
Ziegler
Steven F
SF
Sarfati
Marika
M
Delespesse
Guy
G
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
C498762:CRLF2 protein, human; D016207:Cytokines; D018076:DNA, Complementary; D018121:Receptors, Cytokine; D000094632:Thymic Stromal Lymphopoietin