Biology subjects

Eberl, G.

Publications and source records attributed to Eberl, G..

8 recordsLinked to original sources

bioRxiv2026

ILC3s are Required for Enterocyte Homeostasis to Food Intake

Food provides nutrients that are selectively absorbed by the intestine, but, at the same time, may contain elements that challenge the intestinal barrier and induce post-prandial inflammation (PPI). How PPI is controlled in order to avoid pathological perturbation of homeostasis remains unclear. Here, we report that during fasting, enterocytes increase their absorptive potential and oxidative metabolism, a program that is largely reversed upon food intake of lipids that perturb the intestinal barrier and induce PPI. Such perturbation is countered by ILC3s, in the absence of which PPI increases, program reversal does not occur, and enterocytes engage into excessive oxidative metabolism. This enterocyte state leads to critical hypoglycemia as a consequence of decreased glucose absorption and increased insulinemia, recapitulating the pathological situation found in patients suffering from intestinal damage and sepsis. We hereby uncover a critical function for ILC3s in maintaining enterocyte homeostasis upon challenging food intake.

immunology↗

bioRxiv2026

An elementary model of homeostasis and immunity that generates symbiosis

The immune system was historically defined as a system that provides protection from pathogens. Numerous models have been developed to understand how immunity faces a complex world of microbes that includes pathogens and symbionts, as well as cells of our own self that may develop tumors. Based on the classical assumption that survival depends on internal homeostasis, we have developed a formal model of homeostasis for a host interacting with microbes and self. We propose that such a model must include two fundamental functions: a function that counters change (including tissue repair), and a function that counters the agent of change (such as "immunity" to microbes or self). We show that this elementary model is sufficient to generate symbiosis, and that symbiosis is an emergent property of the host-microbe relationship that does not require the microbe or the host to express "traits of symbiosis". We suggest that the conditions leading to symbiosis contribute to eukaryotic evolution and ontogeny. This model may be further applied to symbiotic interactions between organisms and non-microbial or non-cellular agents of change.

immunology↗

bioRxiv2025

Interleukin-22 in enteroendocrine cells controls early-life gut motility through interactions with the microbiota

The gut microbiota, immune system, and enteric nervous system tightly interact to regulate adult gut physiology. Yet the mechanisms establishing gut physiology during development remain unknown. Here, we report that in developing zebrafish, enteroendocrine cells produce IL-22 in response to microbial signals before lymphocytes populate the gut. In larvae, IL-22 is crucial to set gut microbiota composition, and ghrelin hormone expression to promote gut motility. IL-22 developmental function depends on its ability to modulate gut microbiota, as bacterial transfer from wild-type zebrafish restored gut motility in il22-/- by reestablishing ghrelin hormone expression. Additionally, IL-22-deficient mice show impaired gut motility and reduced ghrelin expression in early life, indicating a conserved function. Altogether, we identify a circuit where enteroendocrine cells regulate gut function via cytokine control of the microbiota, showing how gut physiology is set prior to immune system maturation.

immunology↗

bioRxiv2022

ILC3s select for RORγt+ Tregs and establish tolerance to intestinal microbiota

Microbial colonization of the mammalian intestine elicits inflammatory or tolerogenic T cell responses, but the mechanisms controlling these distinct outcomes remain poorly understood and accumulating evidence indicates that aberrant immunity to intestinal microbiota is causally associated with infectious, inflammatory, and malignant diseases1-8. Here, we define a critical pathway controlling the fate of inflammatory versus tolerogenic T cells that are specific for the microbiota and express the transcription factor ROR{gamma}t. We profiled all ROR{gamma}t+ immune cells at single cell resolution from the intestine-draining lymph nodes of mice and reveal a dominant presence of Tregs and lymphoid tissue-induced (LTi)-like group 3 innate lymphoid cells (ILC3s), which co-localize at interfollicular regions. These ILC3s have interconverting potential with ROR{gamma}t+ extrathymic Aire-expressing cells, abundantly express major histocompatibility complex class II, and are necessary and sufficient to promote microbiota-specific ROR{gamma}t+ Tregs and prevent their expansion as inflammatory T helper (Th)17 cells. This occurs through ILC3-mediated antigen-presentation, interleukin-2 gradients, and v integrin. Finally, single-cell analyses demonstrate that ILC3 and ROR{gamma}t+ Treg interactions are impaired in inflammatory bowel disease. Our results define a novel paradigm whereby ILC3s positively select for antigen specific ROR{gamma}t+ Tregs, and against Th17 cells, to establish immune tolerance to the microbiota and intestinal health.

immunology↗

bioRxiv2021

Metabolic control of type 2 innate lymphoid cells plasticity toward protective type 1-like cells during Mycobacterium tuberculosis infection

Tissue-resident innate lymphoid cells (ILCs) regulate tissue homeostasis, protect against pathogens at mucosal surfaces and are key players at the interface of innate and adaptive immunity. How ILCs adapt their phenotype and function to environmental cues within tissues remains to be fully understood. Here, we show that Mycobacterium tuberculosis infection alters the phenotype and function of immature lung ILC2 toward a protective interferon-{gamma}-producing ILC1-like population. This differentiation is controlled by type 1 cytokines and is associated with a glycolytic program involving the transcription factor HIF1. Collectively, our data reveal how tissue-resident ILCs adapt to type 1 inflammation toward a pathogen tailored immune response.

immunology↗

bioRxiv2019

The impact of gut microbiota on depressive-like behaviors and adult hippocampal neurogenesis requires the endocannabinoid system

Depression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations of the intestinal microbiota, but causality remains yet to be established. Here, using unpredictable chronic mild stress (UCMS) as a mouse model of depression, we show that the UCMS mice display phenotypic alterations -- characterized by an altered gut microbiota composition, a reduced adult hippocampal neurogenesis and a depressive-like behaviors -- which could be transferred from UCMS donors to naive recipient mice by fecal microbiota transplantation. The cellular and behavioral alterations observed in recipient mice were accompanied by a decrease in the endocannabinoid (eCB) signaling due to lower peripheral levels of fatty acid precursors of eCB ligands. The adverse effects of UCMS-transferred microbiota on adult neurogenesis and behavior in naive recipient mice were alleviated by selectively enhancing the central eCB tone or by adding arachidonic acid, a fatty acid precursor of eCB ligands, to the diet. In the gut of both UCMS donors and recipients, the microbiota composition was characterized by a relative decrease in Lactobacilli abundance, and complementation of the UCMS recipient microbiota with a strain of the Lactobacilli genus was sufficient to restore normal eCB brain levels, hippocampal neurogenesis and to alleviate depressive-like behaviors. Our findings provide a mechanistic scenario for how chronic stress, diet and gut microbiota dysbiosis generate a pathological feed-forward loop that contributes to despair behavior via the central eCB system.

neuroscience↗

bioRxiv2019

Innate immune recognition of a bacterial MAMP leads to conditional activation of pro- or anti-inflammatory responses

Microbe-associated molecular patterns (MAMPs) are recognized by pattern recognition receptors (PRRs) of the innate immune system. Flagellin, the primary component of bacterial flagella, is recognized by membrane TLR5 and cytoplasmic NLRC4 receptors, which promote a vigorous pro-inflammatory response typically associated with bacterial infection. However, herein, we report that the nature of the flagellin-induced response is highly dependent on the physiological state of the tissue. Specifically, in the steady state, epithelial cell detection of flagellin orchestrates an anti-inflammatory response mediated by IL-33-dependent type 2 regulatory T cells while, in the context of injury, it induces a pro-inflammatory response mediated by myeloid cells, IL-18 and Th17 cells. Likewise, in the absence of infection, bacterial symbionts expressing high levels of flagellin induce a type 2 response. These data demonstrate that, depending on the inflammatory state of the milieu, MAMPs can function both as immunogens or tolerogens.

immunology↗

bioRxiv2019

Excess calorie intake early in life increases susceptibility to colitis in the adult

Epidemiological data report an association between obesity and inflammatory bowel disease (IBD) 1-3. Furthermore, animal models demonstrate that maternal high fat diet (HFD) and maternal obesity increase susceptibility to IBD in the offsprings 4-8. However, the mechanisms that translate maternal obesity and HFD into increased susceptibility to IBD later in life remain unknown. Here we report that excess calorie intake by neonatal mice, as a consequence of maternal HFD, forced feeding of neonates or low litter competition, lead to an increase, during weaning, in intestinal permeability, expression of pro-inflammatory cytokines and hydrogen sulfide production by the microbiota. In this context, intestinal permeability, cytokine expression and hydrogen sulfide engaged in a mutual positive feedback that imprinted increased susceptibility to colitis in the adult. This pathological imprinting was prevented by the neutralization of IFN{gamma} and TNF, of the production of hydrogen sulphide, or by normalization of intestinal permeability during weaning. Thus, excessive calorie intake by neonates leads to multiple causally-linked perturbations in the intestine that imprint the individual with long term susceptibility to IBD.

immunology↗