Stimulated epithelial cells release TSLP, which activates mast cells to produce IL-13.

Skin and epithelial cells irritated by allergens or by injury produce a cytokine called thymic stromal lymphopoietin (TSLP). This cytokine masterminds a sequence of dendritic cell (DC)–mediated reactions that attract T helper (Th)-2 cells to the hot zone.

In addition to Th2 cells, however, other cells such as mast cells also arrive on the scene. Mast cell recruitment and activation was thought to be dependent on signals from Th2 cells. But, as Allakhverdi et al. now show, mast cells themselves bear TSLP receptors and get directly activated when activated epithelial cells secrete TSLP. Thus, the DC-Th2 mediated "axis of allergy" is bypassed in favor of an innate immune response.

The direct activation of mast cells by TSLP explains the previous finding that mice lacking T cells can develop allergy and inflammation when given TSLP. It might also explain why 20–30% of asthma patients have allergic reactions despite having minimal signs of Th2 induction.

An early involvement of innate immunity in allergy has previously been suspected, according to senior author Guy Delespesse. There are a whole host of clinical observations that show that allergy is a follow-up act to something other than an antigen-specific trigger, he says. A common cold can heighten asthma symptoms, for example, and scratching can worsen eczema. TSLP might thus provide the direct and immediate connection between epithelial trauma and an allergic response.