The signal transducer and activator of transcription 6 (STAT-6) mediates Th2 inflammation and tissue damage in a murine model of peanut-induced food allergy.

INTRODUCTION: Food allergies are inflammatory conditions mediated by Th2 and probably STAT-6 dependent immune responses. OBJECTIVE AND DESIGN: Here we investigated the role of Signal Transducer and Activator of Transcription 6 (STAT-6) in development of inflammation in peanut allergy. METHODS: To induce food allergy, wild-type (WT) and mice deficient for STAT-6 (Stat6-/-) were sensitized with peanut proteins and challenged with peanut seeds. RESULTS: WT animals lost weight and refused the peanut diet, in contrast to Stat6-/- mice, which had a better maintenance of body weight and more regular seeds' consumption. The augmented peanut-specific IgG, IgG1 and IgE in the allergic WT was abolished in Stat6-/- animals that also presented increased IgG2a. There was an overall reduction in the gut mediators in the absence of STAT-6, including those related to inflammatory and Th2 responses, in contrast to a rising counter regulatory and Th1 reaction in Stat-6-/- mice. These animals had IFN-γ and IL-10 similar to WT after the four-week challenge. Most interestingly, Stat-6-/- mice had no intestinal damage, in contrast to WT animals, which had inflammatory infiltrate, tissue destruction, epithelial exulceration, edema, congestion and loss of villous architecture in the small gut segments. CONCLUSIONS: STAT-6 plays an important role in the establishment of the Th2 inflammatory responses and intestinal damage in peanut allergy.