Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses
Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses
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DOI：
10.1016/j.cell.2019.07.047
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发表时间：
2019-08-22
期刊：
影响因子：
64.5
通讯作者：
Hase, Koji
中科院分区：
文献类型：
--
作者：
Nagai, Motoyoshi;Noguchi, Ryotaro;Hase, Koji
营养状况可能影响免疫反应;然而，营养信号如何调节细胞动力学和功能仍然不清楚。在此，我们报告说，暂时禁食大大减少淋巴细胞的数量，减少了50%，在派伊尔集合淋巴结（PP），肠道免疫反应的诱导部位。随后的再喂养似乎恢复了淋巴细胞的数量，但其细胞组成发生了显著变化。大部分生发中心和伊加（+）B细胞在禁食期间通过凋亡而丢失。同时，幼稚B细胞在禁食期间从PP迁移到骨髓，然后在再喂养期间当基质细胞感知营养信号并上调CXCL 13表达以募集幼稚B细胞时返回PP。此外，口服免疫前暂时禁食卵清蛋白取消了抗原特异性伊加的诱导，未能诱导口服耐受，并最终加剧了食物抗原诱导的腹泻。因此，营养信号在维持肠道免疫稳态中至关重要。
Nutritional status potentially influences immune responses; however, how nutritional signals regulate cellular dynamics and functionality remains obscure. Herein, we report that temporary fasting drastically reduces the number of lymphocytes by similar to 50% in Peyer's patches (PPs), the inductive site of the gut immune response. Subsequent refeeding seemingly restored the number of lymphocytes, but whose cellular composition was conspicuously altered. A large portion of germinal center and IgA(+) B cells were lost via apoptosis during fasting. Meanwhile, naive B cells migrated from PPs to the bone marrow during fasting and then back to PPs during refeeding when stromal cells sensed nutritional signals and upregulated CXCL13 expression to recruit naive B cells. Furthermore, temporal fasting before oral immunization with ovalbumin abolished the induction of antigen-specific IgA, failed to induce oral tolerance, and eventually exacerbated food antigen-induced diarrhea. Thus, nutritional signals are critical in maintaining gut immune homeostasis.