title: Requirement of interaction between mast cells and skin dendritic cells to establish contact hypersensitivity.
abstract: The role of mast cells (MCs) in contact hypersensitivity (CHS) remains controversial. This is due in part to the use of the MC-deficient Kit (W/Wv) mouse model, since Kit (W/Wv) mice congenitally lack other types of cells as a result of a point mutation in c-kit. A recent study indicated that the intronic enhancer (IE) for Il4 gene transcription is essential for MCs but not in other cell types. The aim of this study is to re-evaluate the roles of MCs in CHS using mice in which MCs can be conditionally and specifically depleted. Transgenic Mas-TRECK mice in which MCs are depleted conditionally were newly generated using cell-type specific gene regulation by IE. Using this mouse, CHS and FITC-induced cutaneous DC migration were analyzed. Chemotaxis assay and cytoplasmic Ca²⁺ imaging were performed by co-culture of bone marrow-derived MCs (BMMCs) and bone marrow-derived dendritic cells (BMDCs). In Mas-TRECK mice, CHS was attenuated when MCs were depleted during the sensitization phase. In addition, both maturation and migration of skin DCs were abrogated by MC depletion. Consistently, BMMCs enhanced maturation and chemotaxis of BMDC in ICAM-1 and TNF-α dependent manners Furthermore, stimulated BMDCs increased intracellular Ca²⁺ of MC upon direct interaction and up-regulated membrane-bound TNF-α on BMMCs. These results suggest that MCs enhance DC functions by interacting with DCs in the skin to establish the sensitization phase of CHS.
authors: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Atsushi
authors: A
authors: Otsuka
authors: Masato
authors: M
authors: Kubo
authors: Tetsuya
authors: T
authors: Honda
authors: Gyohei
authors: G
authors: Egawa
authors: Saeko
authors: S
authors: Nakajima
authors: Hideaki
authors: H
authors: Tanizaki
authors: Bongju
authors: B
authors: Kim
authors: Satoshi
authors: S
authors: Matsuoka
authors: Takeshi
authors: T
authors: Watanabe
authors: Susumu
authors: S
authors: Nakae
authors: Yoshiki
authors: Y
authors: Miyachi
authors: Kenji
authors: K
authors: Kabashima
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002450:Cell Communication / Q000276:immunology*; D002633:Chemotaxis / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D012867:Skin / Q000276:immunology*
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1