The Mechanisms Involved in Il-2 Production by Regulatory Mast Cells in Chronic Allergic Dermatitis

S A T U R D A Y 208 The Mechanisms Involved in IL-2 Production By Regulatory Mast Cells in Chronic Allergic Dermatitis Alon Hershko, MD, PhD, Itay Moshkovits, Ariel Munitz, PhD, Yoseph A. Mekori, MD, FAAAAI, Pazit Salamon, PhD; Meir Medical Center, Kfar Saba, Israel, Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel, Tel Aviv University, Israel, Meir Hospital, Kfar-Saba, Israel. RATIONALE: We have previously reported that MCs dampen inflammation in oxazolone-induced chronic allergic dermatitis in mice. This suppression occurs by a previously unrecognized regulatory mechanism in which MC’s secrete IL-2 which, in turn, supports regulatory T cell activity at the site of inflammation. However, since IL-2 is not a typical product of MC’s, we sought to define conditions that support its production in the setting of allergic dermatitis. METHODS: Isolated bone marrow-derived MCs (BMMCs) were incubated with various stimulators and IL-2 release was assessed by ELISA. Phosphorylation of signaling molecules was studied by Western blot analysis. Allergic dermatitis was induced in mice by 10 repeated exposures of the ear skin to 0.5% oxazolone in acetone over 4 weeks. Immunohistochemistry was done on paraffin embedded skin specimens. RESULTS: IL-33 is an exclusive inducer of BMMC IL-2 production. Presensitization of cells with IgE further enhanced secretion of IL-2. IL-33 induced phosphorylation of the MAPKs family members ERK, p38 and JNK, and the inhibitors for these MAPKs dampened IL-2 release. The levels of IL-33 in ear homogenates from oxazolone-treated mice was greater than those of na€ive ears. Staining of ears disclosed in vivo co-localization of IL-33 and MC in ears with dermatitis. CONCLUSIONS: MC-derived IL-2 was previously shown to stimulate Tregs in allergic dermatitis, and here we show that its production is stimulated by IL-33. In dermatitis, the levels of IL-33 increase and it colocalizes with MC. We suggest that IL-33 is a pivotal player in the induction of regulatory MC’s.