Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses

Motoyoshi Nagai, Ryotaro Noguchi, Daisuke Takahashi, Takayuki Morikawa, Kouhei Koshida, S. Komiyama, Narumi Ishihara, Takahiro Yamada, Yuki I. Kawamura, Kisara Muroi, K. Hattori, Nobuhide Kobayashi, Yumiko Fujimura, Masato Hirota, Ryohtaroh Matsumoto, Ryo Aoki, Miwa Tamura-Nakano, Machiko Sugiyama, Tomoya Katakai, Shintaro SatoK. Takubo, T. Dohi, Koji Hase

Research output: Contribution to journalArticle

20 Citations (Scopus)

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. Temporary fasting drastically reduces the levels of B cells in Peyer's patches, with germinal center B cells undergoing apoptosis and naive cells migrating to the bone marrow and only egressing upon refeeding.

Original languageEnglish
Pages (from-to)1072-1087.e14
JournalCell
Volume178
Issue number5
DOIs
Publication statusPublished - 2019 Aug 22

Keywords

  • B cell
  • CXCL13
  • IgA
  • Immunometabolism
  • Peyer's patch
  • bone marrow
  • fasting
  • mTOR signaling
  • mucosal immunity
  • nutritional signals
  • stroma cell

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Nagai, M., Noguchi, R., Takahashi, D., Morikawa, T., Koshida, K., Komiyama, S., Ishihara, N., Yamada, T., Kawamura, Y. I., Muroi, K., Hattori, K., Kobayashi, N., Fujimura, Y., Hirota, M., Matsumoto, R., Aoki, R., Tamura-Nakano, M., Sugiyama, M., Katakai, T., ... Hase, K. (2019). Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses. Cell, 178(5), 1072-1087.e14. https://doi.org/10.1016/j.cell.2019.07.047