title: Non-classical MHC I-E negatively regulates macrophage activation and Th17 cell development in NOD mice.
abstract: Transgenic expression of I-E molecules prevents diabetes in NOD mice. So far, the precise role of these non-classical MHC II molecules remains elusive. Here, we showed that transgenic expression of I-E(k) alpha 16 molecule in NOD mice selectively reduced Th17 cells in the thymus and pancreatic draining lymph nodes. The reduction in Th17 cells was associated with both attenuated IL-6 production and decreased activation of macrophages. Mechanistically, transgenic expression of the I-E molecule diminished expression of intracellular classical MHC II molecule and led to impaired TLR4-mediated signaling. In contrast to classical MHC II molecule, this non-classical MHC II molecule negatively regulates the inflammatory responses of macrophages. Altogether, our study reveals a novel regulatory role of I-E molecules in modulating inflammatory immune responses.
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Yang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, China.
authors.forename: Nining
authors.initials: N
authors.lastname: Guo
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, China.
authors.forename: Juhao
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, China.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Leng
mesh_terms: D000818:Animals; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D015534:Trans-Activators
chemical_list: D015850:Interleukin-6; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D015534:Trans-Activators