Mannan-binding lectin, a serum collectin, suppresses T-cell proliferationvia direct interaction with cell surface calreticulin and inhibition of proximal T-cell receptorsignaling
Mannan-binding lectin, a serum collectin, suppresses T-cell proliferationvia direct interaction with cell surface calreticulin and inhibition of proximal T-cell receptorsignaling
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甘露聚糖结合凝集素（一种血清集合素）通过与细胞表面钙网蛋白直接相互作用并抑制近端 T 细胞受体信号传导来抑制 T 细胞增殖
DOI：
10.1096/fj.201601200rr
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Daming Zuo
中科院分区：
文献类型：
--
作者：
Na Zhao;Jie Wu;Simin Xiong;Liyun Zhang;Xiao Lu;Shangliang Chen;Qifeng Wu;Hailan Wang;Ying Liu;Zhengliang Chen;Daming Zuo
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. FASEB J. 31, 2405–2417 (2017). www.fasebj.org
