Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses

禁食-再进食影响免疫细胞动力学和粘膜免疫反应

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作者:Motoyoshi Nagai, Ryotaro Noguchi, Daisuke Takahashi, Takayuki Morikawa, Kouhei Koshida, Seiga Komiyama, Narumi Ishihara, Takahiro Yamada, Yuki I Kawamura, Kisara Muroi, Kouya Hattori, Nobuhide Kobayashi, Yumiko Fujimura, Masato Hirota, Ryohtaroh Matsumoto, Ryo Aoki, Miwa Tamura-Nakano, Machiko Sugiy

Abstract

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 ∼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.

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