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

TLDR

Epithelial cell‑derived thymic stromal lymphopoietin (TSLP) may initiate asthma or atopic dermatitis through a dendritic cell‑mediated Th2 response. The study investigates how TSLP could initiate and aggravate allergic inflammation without T lymphocytes or IgE via the innate immune system. TSLP, together with IL‑1 and TNF, induces high Th2 cytokine production by mast cells, and is released by epithelial cells upon microbial exposure, injury, or inflammatory cytokines, suggesting that epithelial cell‑derived TSLP activates mast cells to drive intrinsic atopic disease and explain infection or scratching exacerbations.

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.