Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses

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.

Differential regulation of the immune system in a brain-liver-fats organ network during short term fasting

“…While our study was not purposed to decipher the molecular communication between organs or to investigate the migratory behaviors or composition of immune cells under fasting conditions [4][5][6], our study highlights the centrality of immune-transcriptomic modulations during STF. Using a combinatorial data analysis approach, we provide evidence for the existence of an organ network, formed by the similarities of their biological processes, and the prominent role of the immune system in sensing and modulating systemic homeostatic perturbations in the absence of infection.…”

“…However, the mechanisms underlying fasting-induced effects on the immune system remain largely unknown and only recently started to be elucidated [83]. Three recent studies demonstrated that monocytes, naïve B cells, and memory CD8 T cells use bone marrow as a refuge during periods of energy reduction to maintain systemic immune-responsiveness [4][5][6]. These studies also provided new insights into the integrated immunometabolic response in a state of energy deprivation.…”

“…These various forms of reduction in food consumption have many beneficial effects on health, including weight reduction, amelioration of autoimmune diseases, and increased lifespan [2,3]. In line with this, a triad of recent studies demonstrated the ability of different forms of fasting on changing the level and functions of the various immune cell types [4][5][6]. Recently, the interest and applicability of fasting to treat various conditions are as such that they have generated momentum in clinical trials [7][8][9].…”

Metabolic determinants of lupus pathogenesis

“…73 Upon re-introduction of calories, naive B cells migrated back to Peyer's patches. 73 Therefore, it is possible that CR may modulate B cell populations and autoantibody levels in lupus. Within the innate immune system, circulating monocyte frequency and functionality were reduced in response to fasting in both humans and mice, which improved clinical parameters in EAE.…”

Identification and local manipulation of bone marrow vasculature during intravital imaging

“…tion and HSPC homing are reportedly important to maintain the immune response and hematopoiesis, respectively 38,39 . To assess a potential role for NE in blood cell migration into the BM, we first performed TCA of NE and 10 minutes later injected mice i.v.…”