Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells

Journal of Experimental Medicine - Tập 204 Số 2 - Trang 253-258 - 2007
Zoulfia Allakhverdi1, Michael R. Comeau2, Heidi K. Jessup2, Bo‐Rin Park Yoon2, A W Brewer2, Suzanne Chartier3, Nicole Paquette3, Steven F. Ziegler4, Marika Sarfati5, G Delespesse1
11Laboratory on Allergy
24Inflammation Research, Amgen Inc., Seattle, WA 98119
33Dermatology Service, Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada
45Department of Immunology, Benaroya Research Institute, Virginia Mason Medical Center, Seattle, WA 98101
52Laboratory on Immunoregulation, CHUM Research Center,

Tóm tắt

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.

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