title: CD1d expressed in mast cell surface enhances IgE production in B cells by up-regulating CD40L expression and mediator release in allergic asthma in mice.
abstract: Mast cells play important roles via FcεRI-mediated activation in allergic asthma. A nonpolymorphic MHC I-like molecule CD1d, which is mainly expressed in APCs, presents glycolipid Ag to iTCR on iNKT cells and modulates allergic responses. This study aimed to investigate the role of CD1d on IgE production and mast cell activation related to allergic asthma. Bone marrow-derived mast cells (BMMCs) from C57BL/6 Wild type (WT) or KO (CD1d(-/-)) mice were activated with Ag/Ab (refer to WT-act-BMMCs and KO-act-BMMCs, respectively) or α-Galactosylceramide (WT-αGal-BMMCs, KO-αGal-BMMCs) in the presence of iNKT cells. WT, KO or BMMC-transferred KO mice were sensitized and/or challenged by OVA or α-Gal to induce asthma. KO-act-BMMCs reduced intracellular Ca(2+) levels, expression of signaling molecules (Ras, Rac1/2, PLA2, COX-2, NF-κB/AP-1), mediator release (histamines, leukotrienes and cytokines/chemokines), and total IgE levels versus the corresponding WT-BMMCs. KO mice reduced total and OVA-specific serum IgE levels, number of mast cells, recruiting molecules (CCR2/CCL2, VCAM-1, PECAM-1), expression of tryptase, c-kit, CD40L and cytokine mRNA, co-localization of c-kit and CD1d or iNKT cells in BAL cells or lung tissues, and PCA responses, compared with the corresponding WT mice. BMMC-transferred KO-both mice showed the restoration of all allergic responses versus KO-both mice (Ag/Ab reaction plus α-Gal). KO-αGal-BMMCs or KO-αGal mice did not show any responses. Our data suggest that CD1d-expressed mast cells may function as APC cells for iNKT cells and exacerbate airway inflammation and remodeling through up-regulating IgE production via B cell Ig class switching and mediator release in mast cells of OVA-challenged mice.
authors: Department of Pharmacology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors: Gwan Ui
authors: GU
authors: Hong
authors: Department of Pharmacology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors: Nam Goo
authors: NG
authors: Kim
authors: Department of Pathology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors: Tae Jin
authors: TJ
authors: Kim
authors: Department of Pharmacology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea. Electronic address: jyro426@skku.edu.
authors: Jai Youl
authors: JY
authors: Ro
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000378:metabolism*; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D023201:CD40 Ligand / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000473:pathology; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000633:toxicity*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D055610:Antigens, CD1d; D016207:Cytokines; D023201:CD40 Ligand; D007073:Immunoglobulin E; D010047:Ovalbumin; D002118:Calcium
keywords: Allergic asthma; CD1d; IgE; Mast cells; iNKT cells