Mannan-binding lectin, a serum collectin, suppresses T-cell proliferation via direct interaction with cell surface calreticulin and inhibition of proximal T-cell receptor signaling

作者：Zhao, Na; Wu, Jie; Xiong, Simin; Zhang, Liyun; Lu, Xiao; Chen, Shangliang; Wu, Qifeng; Wang, Hailan; Liu, Ying; Chen, Zhengliang^*; Zuo, Daming^*

来源：The FASEB Journal, 2017, 31(6): 2405-2417.

DOI：10.1096/fj.201601200RR

• T-cell activation
• cell cycle
• silicosis

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 ofMBL 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 ofMBLand calreticulin (CRT) expressed on theT-cell surface. The neutralizing antibody against CRT abrogated MBL mediated suppression of T-cell proliferation, suggesting thatMBL down-modulates T-cell proliferation via cell surface CRT. We further demonstrated that the feature of MBL-mediatedT-cell suppression is shared by other serum collectins (e.g., C1q and collectin 11). The concentrations of MBL correlated negatively with in vivo T-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.

• 出版日期2017-6
• 单位山西医科大学; 广东省人民医院; 南方医科大学