TRAF3IP3, a novel autophagy up-regulated gene, is involved in marginal zone B lymphocyte development and survival
TRAF3IP3, a novel autophagy up-regulated gene, is involved in marginal zone B lymphocyte development and survival
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DOI：
10.1111/cei.12658
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发表时间：
2015-10-01
影响因子：
4.6
通讯作者：
Zhao, H.
中科院分区：
文献类型：
--
作者：
Peng, S.;Wang, K.;Zhao, H.
肿瘤坏死因子受体相关因子3（TRAF 3）相互作用蛋白3（TRAF 3 IP 3;也称为T3 JAM）在免疫器官和组织中特异性表达。为了研究TRAF 3 IP 3对免疫的影响，我们产生了Traf 3 ip 3敲除（KO）小鼠。有趣的是，这些小鼠表现出普通淋巴祖细胞（CLP）数量的显著减少和骨髓中B细胞发育的抑制。此外，Traf 3 ip 3 KO小鼠在脾脏中缺乏边缘区（MZ）B细胞。Traf 3 ip 3 KO小鼠还表现出血清天然抗体量减少和对三硝基苯酚（TNP）-Ficoll抗原的T细胞非依赖性II型（TI-II）应答受损。此外，我们的研究结果表明，Traf 3 ip 3通过ATG 16 L1结合基序促进自噬，并且从突变小鼠分离的MZ B细胞显示出降低的自噬水平和高的凋亡率。这些结果表明TRAF 3 IP 3通过上调自噬从而促进TI-II免疫应答而有助于MZ B细胞存活。
Tumour necrosis factor receptor-associated factor 3 (TRAF3) interacting protein 3 (TRAF3IP3; also known as T3JAM) is expressed specifically in immune organs and tissues. To investigate the impact of TRAF3IP3 on immunity, we generated Traf3ip3 knock-out (KO) mice. Interestingly, these mice exhibited a significant reduction in the number of common lymphoid progenitors (CLPs) and inhibition of B cell development in the bone marrow. Furthermore, Traf3ip3 KO mice lacked marginal zone (MZ) B cells in the spleen. Traf3ip3 KO mice also exhibited a reduced amount of serum natural antibodies and impaired T cell-independent type II (TI-II) responses to trinitrophenol (TNP)-Ficoll antigen. Additionally, our results showed that Traf3ip3 promotes autophagy via an ATG16L1-binding motif, and MZ B cells isolated from mutant mice showed a diminished level of autophagy and a high rate of apoptosis. These results suggest that TRAF3IP3 contributes to MZ B cell survival by up-regulating autophagy, thereby promoting the TI-II immune response.