Skin‐infiltrating basophils promote atopic dermatitis‐like inflammation via IL‐4 production in mice

Background Patients with atopic dermatitis (AD) often show the infiltration of basophils in the affected skin. Because basophils represent only a minor fraction among cellular infiltrates in the skin lesion, the functional significance of skin‐infiltrating basophils in AD pathogenesis remains ill‐defined. In this study, we aimed to clarify the role of basophils and their effector molecules triggering skin inflammation in oxazolone (OX)‐induced murine model of AD. Methods A panel of mouse strains were sensitized and repeatedly challenged with topical applications of OX to induce AD‐like skin inflammation. Both local and systemic Th2 immune responses were analyzed. Results Basophils progressively accumulated in the skin lesion but barely in draining lymph nodes (LNs). When basophils were depleted during the elicitation phase, skin inflammation was ameliorated while Th2 cell differentiation in draining LNs remained intact. The expression of IL‐4 was highly upregulated in the affected skin, and basophils turned out to be the major producers of IL‐4 among cellular infiltrates, suggesting the involvement of basophil‐derived IL‐4 in the Th2 skin inflammation. Indeed, basophil‐specific IL‐4‐deficient mice displayed attenuated skin inflammation with a marked reduction of IL‐4 in the skin lesion, even though cutaneous basophil infiltration and serum levels of IgE remained intact. Conclusions Skin‐infiltrating basophils promoted OX‐induced AD‐like skin inflammation through their local production of IL‐4, rather than the induction of Th2 cell differentiation in draining LNs. This study suggests that the selective targeting of basophils could be a beneficial strategy in the treatment of a certain type of AD. Basophils infiltrated the OX‐induced AD‐like skin lesion but barely draining LNs, and they were major IL‐4 producers in the affected skin. Basophil‐specific IL‐4‐deficient mice showed ameliorated skin inflammation even though serum levels of IgG1/IgE remained intact. Skin‐infiltrating basophils play a crucial role in the development of OX‐induced AD‐like skin inflammation through local IL‐4 production, independently of LN Th2 cell differentiation. Abbreviations: AD, atopic dermatitis; BAS IL‐4 KO, basophil‐specific IL‐4‐deficient mouse; OX, oxazolone.