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Cell ; 178(5): 1072-1087.e14, 2019 08 22.
Article in English | MEDLINE | ID: mdl-31442401

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.


Subject(s)
B-Lymphocytes/physiology , Immunity, Mucosal , Animals , Antigens/immunology , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Bone Marrow/immunology , Bone Marrow/metabolism , Chemokine CXCL13/genetics , Chemokine CXCL13/metabolism , Fasting , Gene Expression Regulation , Glycolysis , Immunoglobulin A/metabolism , Male , Mice , Mice, Inbred BALB C , Nutritional Status , Ovalbumin/immunology , Peyer's Patches/immunology , Peyer's Patches/metabolism , Peyer's Patches/pathology , Receptors, CXCR5/genetics , Receptors, CXCR5/metabolism , Signal Transduction , Stromal Cells/cytology , Stromal Cells/metabolism , TOR Serine-Threonine Kinases/metabolism
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