Cell
Volume 178, Issue 5, 22 August 2019, Pages 1072-1087.e14
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Article
Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses

https://doi.org/10.1016/j.cell.2019.07.047Get rights and content
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Highlights

  • Fasting drastically reduces lymphocyte levels in Payer’s patches

  • Naive B cells migrate to bone marrow during fasting and then back upon refeeding

  • Nutritional signals are essential to maintain CXCL13 expression by stromal cells

  • Fasting causes GC B cell death and attenuates antigen-specific IgA response

Summary

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.

Keywords

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

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