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Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses
- Nagai, Motoyoshi, Noguchi, Ryotaro, Takahashi, Daisuke, Morikawa, Takayuki, Koshida, Kouhei, Komiyama, Seiga, Ishihara, Narumi, Yamada, Takahiro, Kawamura, Yuki I., Muroi, Kisara, Hattori, Kouya, Kobayashi, Nobuhide, Fujimura, Yumiko, Hirota, Masato, Matsumoto, Ryohtaroh, Aoki, Ryo, Tamura-Nakano, Miwa, Sugiyama, Machiko, Katakai, Tomoya, Sato, Shintaro, Takubo, Keiyo, Dohi, Taeko, Hase, Koji
- Cell 2019 v.178 no.5 pp. 1072-1087.e14
- B-lymphocytes, Peyer's patches, apoptosis, bone marrow, chemokine CXCL13, diarrhea, digestive system, fasting, homeostasis, immune response, immunoglobulin A, lymph nodes, mucosal immunity, nutritional status, oral vaccination, ovalbumin, refeeding, stromal cells
- 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.