ILC2 activation by keratinocyte derived IL 25 drives IL 13 production at sites of allergic skin inflammation
Background Atopic dermatitis skin lesions demonstrate increased expression of IL 25 by keratinocytes and increased numbers of type 2 innate lymphoid cells (ILC2s) that express high levels of IL 25 receptor (IL 25R) IL 13 is expressed in atopic dermatitis skin lesions and plays an important role in pathogenesis of the disease. Objective Our aim was to determine the role of IL 25 and ILC2s in a mouse model of antigen driven allergic skin inflammation. Methods Wild type mice; mice that express an Il13 driven enhanced green fluorescent protein; and mice that lack IL 25R, IL 25 in keratinocytes, or IL 13 or IL 25R in ILC2s were subjected to acute or chronic epicutaneous sensitization with ovalbumin. Sensitized skin was examined by histology for epidermal thickening. Cellular infiltrates were analyzed for surface markers and intracellular expression of enhanced green fluorescent protein by flow cytometry. Gene expression was quantitated by RT quantitative PCR. Result In both acute and chronic antigen driven allergic skin inflammation, signaling by keratinocyte derived IL 25 in ILC2s is important for epidermal hyperplasia, dermal infiltration by CD4+ T cells, and cutaneous expression of Il13 and the IL 13 dependent TH2 cell attracting chemokines Cc17 and Ccl22. ILCs are the major source of IL 13 in acutely sensitized mouse skin, whereas T cells are its major source in chronically sensitized mouse skin. Conclusion ILC2 activation by IL 25 is essential for IL 13 expression at sites of allergic skin inflammation.
The Journal of allergy and clinical immunology