title: Mannan-binding lectin, a serum collectin, suppresses T-cell proliferationviadirect interaction with cell surface calreticulin and inhibition of proximal T-cell receptor signaling.
abstract: Mannan binding lectin (MBL), initially reported to activate the complement pathway, is also known to be involved in the pathogenesis of autoimmune diseases. We report a thus far unknown function of MBL as a suppressor of T-cell activation. MBL markedly inhibited T-cell proliferation induced by anti-CD3 and anti-CD28 antibodies. Moreover, the presence of MBL during T-cell priming interfered with proximal T-cell receptor signaling by decreasing phosphorylation of Lck, ZAP-70, and LAT. MBL bound to T cells through interaction between the collagen-like region of MBL and calreticulin (CRT) expressed on the T-cell surface. The neutralizing antibody against CRT abrogated MBL-mediated suppression of T-cell proliferation, suggesting that MBL down-modulates T-cell proliferationviacell surface CRT. We further demonstrated that the feature of MBL-mediated T-cell suppression is shared by other serum collectins (e.g.,C1q and collectin 11). The concentrations of MBL correlated negatively within vivoT-cell activation status in patients with early-stage silicosis. Furthermore, MBL efficiently inhibited activation and proliferation of autoreactive T cells derived from patients with silicosis, indicating that MBL serves as a negative feedback control of the T-cell responses.-Zhao, N., Wu, J., Xiong, S., Zhang, L., Lu, X., Chen, S., Wu, Q., Wang, H., Liu, Y., Chen, Z., Zuo, D. Mannan-binding lectin, a serum collectin, suppresses T-cell proliferationviadirect interaction with cell surface calreticulin and inhibition of proximal T-cell receptor signaling.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.|Department of Occupational Medicine, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Occupational Medicine, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, China.|School of Public Health, Shanxi Medical University, Taiyuan, China; and.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Simin
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Shangliang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Occupational Medicine, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Occupational Medicine, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, China.|School of Public Health, Shanxi Medical University, Taiyuan, China; and.
authors.forename: Hailan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; zhlchen@smu.edu.cn.|Guangdong Provincial Key Laboratory of Proteomics, Southern Medical University, Guangzhou, China.
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; zdaming@smu.edu.cn.|Guangdong Provincial Key Laboratory of Proteomics, Southern Medical University, Guangzhou, China.
authors.forename: Daming
authors.initials: D
authors.lastname: Zuo
mesh_terms: D037282:Calreticulin / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D037601:Mannose-Binding Lectin / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell; D015398:Signal Transduction; D012829:Silicosis; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D037282:Calreticulin; D037601:Mannose-Binding Lectin; D011948:Receptors, Antigen, T-Cell
keywords: T-cell activation; cell cycle; silicosis