40 Contribution of IL-33 and Nuocyte to Experimental Allergic Dermatitis

BACKGROUND: IL-33 is a member of the IL-1 family cytokines and the ligand of ST2 (IL-33R alpha chain). IL-33 stimulates Th2 cells, basophils, mast cells, and nuocyte, a recently discovered new lymphocyte, to produce various cytokines. We have previously shown that the serum level of IL-33 is significantly elevated in patients with Japanese cedar pollinosis(1) and IL-33 has the potential to induce Th2 cytokine-mediated allergic conjunctivitis(2). As these results suggest that IL-33 may also have some relations to allergic dermatitis, we now examined the pathological role of IL-33 in dermatitis. First, we investigated an immediate reaction of skin by challenging BALB/c mice with DNFB repeatedly. We also tested the involvement of natural helper cells (nuocyte) in dermatitis of NC/Nga mice. METHODS: (1) Wild-type BALB/c mice or ST2 KO mice were sensitized and repeatedly challenged with DNFB on the left ear at 1 week intervals. When they are challenged 4 or 5 times, the ear shows biphasic (bimodal) responses which consist of an immediate phase and a delayed-type reaction. (2) When NC/Nga mice are raised in conventional (non-SPF) circumstances, skin lesions that are clinically similar to human atopic dermatitis spontaneously appears on the skin. We separated lymphocytes from the inflamed skin of NC/Nga mice using collagenase I (Sigma-Aldrich) and counted the numbers of nuocytes (ST2+/Sca-1+/lineage marker-negative) by FACS. RESULTS: (1) The reactions were hapten specific. Wild-type BALB/c mice showed both immediate and delayed-type reactions, whereas ST2 KO mice did not show any immediate reaction. (2) When IL-33 was administered subcutaneously, NC/Nga mice showed increase of serum IgE level. The number of nuocytes in inflamed skin of NC/Nga mice significantly increased compared to non-inflamed skin. The nuocytes showed very weak expression of ST2 in non-inflamed skin, whereas the expression of ST2 in inflamed skin was very significant. CONCLUSIONS: These results suggest that IL-33 may have an important role in the mechanism of immediate contact hypersensitivity, and nuocytes may contribute to the development of atopic dermatitis-like skin lesion in NC/Nga mice.