Citation

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Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses

Nagai, M;Noguchi, R;Takahashi, D;Morikawa, T;Koshida, K;Komiyama, S;Ishihara, N;Yamada, T;Kawamura, YI;Muroi, K;Hattori, K;Kobayashi, N;Fujimura, Y;Hirota, M;Matsumoto, R;Aoki, R;Tamura-Nakano, M;Sugiyama, M;Katakai, T;Sato, S;Takubo, K;Dohi, T;Hase, K;

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. Copyright 2019 Elsevier Inc. All rights reserved.