T regulatory cells and B cells cooperate to form a regulatory loop that maintains gut homeostasis and suppresses dextran sulfate sodium-induced colitis.
T regulatory cells and B cells cooperate to form a regulatory loop that maintains gut homeostasis and suppresses dextran sulfate sodium-induced colitis.
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T 调节细胞和 B 细胞合作形成调节环，维持肠道稳态并抑制硫酸葡聚糖钠诱导的结肠炎
DOI：
10.1038/mi.2015.20
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发表时间：
2015-11
影响因子：
8
通讯作者：
Chu Y
中科院分区：
文献类型：
--
作者：
Wang L;Ray A;Jiang X;Wang JY;Basu S;Liu X;Qian T;He R;Dittel BN;Chu Y
肠相关淋巴组织（GALT）中存在的调节性T细胞（TCLs）和B细胞均参与结肠炎的消退。然而，这些细胞的功能如何协调仍然是难以捉摸的。我们使用葡聚糖硫酸钠（DSS）诱导的结肠炎模型结合基因修饰小鼠来监测结肠炎的进展，并同时检查TcB和B细胞的数量以及伊加抗体的产生。我们发现，DSS治疗的小鼠在缺乏B细胞的情况下表现出更严重的结肠炎，并且B细胞的过继转移减轻了疾病。此外，IL-10（-/-）B细胞的转移也减弱了结肠炎，表明B细胞通过白细胞介素-10（IL-10）非依赖性途径抑制结肠炎。此外，Tcl 3的抗体耗竭导致结肠炎恶化。有趣的是，在结肠炎期间，B细胞缺陷小鼠中的GALT T细胞数量显著减少，并且将B细胞过继转移到这些小鼠中恢复了Treg数量，表明B细胞有助于Treg稳态。我们还发现，B细胞诱导的增殖TCL 4，这反过来又促进B细胞分化为IgA产生的浆细胞。这些结果表明，B细胞和TCLs相互作用和合作，以防止可能导致结肠炎的过度免疫反应。
Regulatory T cells (Tregs) and B cells present in gut-associated lymphoid tissues (GALT) are both implicated in the resolution of colitis. However, how the functions of these cells are coordinated remains elusive. We used the dextran sulfate sodium (DSS)-induced colitis model combined with gene-modified mice to monitor the progression of colitis, and simultaneously examine the number of Tregs and B cells, and the production of IgA antibodies. We found that DSS-treated mice exhibited more severe colitis in the absence of B cells, and that the adoptive transfer of B cells attenuated the disease. Moreover, the transfer of IL-10(-/-) B cells also attenuated colitis, suggesting that B cells inhibited colitis through an interleukin-10 (IL-10)-independent pathway. Furthermore, antibody depletion of Tregs resulted in exacerbated colitis. Intriguingly, the number of GALT Tregs in B cell-deficient mice was significantly decreased during colitis and the adoptive transfer of B cells into these mice restored the Treg numbers, indicating that B cells contribute to Treg homeostasis. We also found that B cells induced the proliferation of Tregs that in turn promoted B-cell differentiation into IgA-producing plasma cells. These results demonstrate that B cells and Tregs interact and cooperate to prevent excessive immune responses that can lead to colitis.