title: IL-33 promotes MHC class II expression in murine mast cells.
abstract: Mast cells (MCs), recognized as tissue-resident cells of hematopoietic origin, are involved in cellular and pathological manifestations of allergic disorders including atopic dermatitis. IL-33, a member of the IL-1 cytokine family, activates Th2-type immune responses, and promotes the degranulation and maturation of MCs. However, it is uncertain whether IL-33 treatment induces mature mast cells to acquire the characteristics of the monocyte-dendritic cell lineage.We investigated the effect of IL-33 on the MHC class II expression and function of murine mast cells. IL-33-treated mature murine bone marrow-derived mast cells (BMMCs) were analyzed by FACS, real-time PCR, chromatin immunoprecipitation (ChIP) assay, and Western blotting. The morphology and degranulation activity of BMMCs and T-cell activation by BMMCs were also examined. BMMCs treated with IL-33 for 10 days induced cell surface expression of the MHC class II protein, whereas the expression of FcεRI and c-kit was not affected by IL-33. The expression of CIITA, driven from pIII and pIV, was up-regulated in IL-33-treated BMMCs. The amount of PU.1 mRNA and protein significantly increased in IL-33-treated BMMCs. The ChIP assay showed PU.1 binding to CIITA pIII, and enhanced histone acetylation due to IL-33 treatment. Syngeneic T cells were activated by co-culture with IL-33-treated BMMCs, although the expression of the co-stimulatory molecules, CD40, CD80, CD86, and PDL-1, was not detected. Mast cells express MHC class II after prolonged exposure to IL-33, probably due to enhanced recruitment of PU.1 to CIITA pIII, resulting in transactivation of CIITA and MHC class II. IL-33 is an important cytokine in allergic disorders. Mast cells have the ability to express MHC class II after prolonged exposure to IL-33 in a murine model. IL-33 holds a key to understanding the etiology of atopic dermatitis.
authors.affiliation: Department of Dermatology, Tokyo Medical University 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Dermatology, Tokyo Medical University 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Chizu
authors.initials: C
authors.lastname: Egusa
authors.affiliation: Department of Dermatology, Tokyo Medical University 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Department of Dermatology, Tokyo Medical University 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Numata
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University School of Medicine 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nakano
authors.affiliation: Department of Biological Science and Technology, Tokyo University of Science 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Nishiyama
authors.affiliation: Department of Dermatology, Tokyo Medical University 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Tsuboi
keywords: IL-33; MHC class II; MHC class II transactivator (CIITA); PU.1; mast cells