Rational T cell repertoire allocation to control the gut microbiota

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   Profiling of intestinal T cells reveals antigen-specific dependency on early-life programming for the generation of microbiota-reactive Tregs

   L. Vetter, J. Witchley, S. Ahn et al. · 2026 · bioRxiv · Pas encore résumé

   Résumé scientifique

   The generation of appropriate responses to the intestinal microbiota is an essential aspect of immune homeostasis. Studies of microbes that elicit stereotyped, antigen-specific CD4 T cell responses support the view that immune recognition of the microbiota is specific, relatively limited, and largely skewed toward Tregs, but recent profiling efforts have suggested that recognition of the microbiota may be broader and less regulatory. Such studies have mostly tracked responses to single antigens or used mice that acquire their microbiota after weaning, which has made it difficult to generalize the rules that govern microbiota-mediated T cell responses. Here we comprehensively profile, for the…

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   A microbiome-reactive TMIGD2hi Th17 subset is spatially enriched at the intestinal epithelium and expanded in inflammatory bowel disease.

   T. K. Pedersen, Tanvi Jain, Å. Segerstolpe et al. · 2026 · Immunity · Pas encore résumé

   Résumé scientifique

   Subsets of intestinal CD4+ T cells directly recognize commensal bacteria and coordinate tolerance versus protective immunity. Our limited understanding of CD4+ T cell specificities and corresponding functional phenotypes has created a barrier to deciphering the mechanisms of mucosal homeostasis and inflammation mediated by the adaptive immune system. To address this, we leveraged an immunodominant Bacteroidetes epitope in SusC to perform single-cell profiling of the SusC-specific and total CD4+ T cell landscapes in intestinal tissues of patients with inflammatory bowel disease (IBD). By analyzing phenotypes and T cell receptor specificities in parallel, we uncovered phenotypic diversificatio…

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   The influence of T cell development on pathogen specificity and autoreactivity

   Andrej Kosmrlj, Mehran Kardar, Arup K. Chakraborty · 2011 · J. Stat. Phys. 149 (2012) 203-219 · Résumé IA disponible

   Résumé scientifique

   T cells orchestrate adaptive immune responses upon activation. T cell activation requires sufficiently strong binding of T cell receptors on their surface to short peptides derived from foreign proteins bound to protein products of the major histocompatibility (MHC) gene products, which are displayed on the surface of antigen presenting cells. T cells can also interact with peptide-MHC complexes, where the peptide is derived from host (self) proteins. A diverse repertoire of relatively self-tolerant T cell receptors is selected in the thymus. We study a model, computationally and analytically, to describe how thymic selection shapes the repertoire of T cell receptors, such that T cell recept…

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   Weaning imprints a hybrid cytotoxic-regulatory identity on intestinal CD4+ T lymphocytes

   Marina Schernthanner, R. Gokhale, Alexandra Thoms et al. · 2026 · bioRxiv · Pas encore résumé

   Résumé scientifique

   The intestinal immune system must adapt as the neonatal gut shifts from milk to solid food and becomes densely colonized. How the T cell compartment is established under these conditions remains unclear. Using fate-mapping to timestamp naïve T cells, with imaging, transcriptomic, and repertoire analyses, we tracked them from suckling to adulthood. Intestinal T cell entry peaked at weaning, coinciding with relocation from crypts to villi guided by the tissue microenvironment and, partly, the microbiota. T cells timestamped at suckling persisted into adulthood and, at weaning, adopted a transient cytotoxic-regulatory state in the lamina propria, with granzyme B expression microbiota-dependent …

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   Antibody-mediated immune surveillance as an organizing axis of gut microbiota structure

   Simeon Nthuku, D. Sterlin, N. Pons et al. · 2026 · Microbiome · Pas encore résumé

   Résumé scientifique

   The symbiotic interplay between the immune system and the endogenous microbiome is essential for maintaining homeostasis. However, most microbiome research focuses primarily on associations between disease and microbial composition, often overlooking host–microbiota interactions as a defining component of health and pathology. The gut microbiota is continuously monitored by the immune system, particularly via immunoglobulin A (IgA), which shapes microbial communities by selectively targeting specific taxa. Despite its central role, IgA-mediated immune surveillance has rarely been formalized as a quantitative axis in microbiota analysis, limiting our understanding of how host–microbe interact…

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   Host genetics determines the fate of the Lactobacillaceae population in the small intestine

   Helen Beilinson Lietuvninkas, M. Coyne, Kiera Bass et al. · 2026 · bioRxiv · Pas encore résumé

   Résumé scientifique

   Whereas innate pattern recognition receptors bind evolutionary conserved moieties shared by diverse groups of microbes, control over closely related microorganisms is likely based on different principles and can be sensitive to genetic variation of the host. While the influence of host genetics on intestinal microbiome composition has been growing in appreciation, understanding of polymorphic mechanisms that regulate individual bacterial lineages requires complex approaches. Using gnotobiotic mouse monocolonized with Ligilactobacillus murinus (ASF361), we found that C57BL/6J (B6) mice harbored significantly more intestinal ASF361 (or other Lactobacillaceae genera) than did BALB/cJ (BALB/c) m…

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   A defined microbial community remodels host metabolism and pathogen resistance in Caenorhabditis elegans

   N. Dennis, Laura M. Freeman, M. Vazquez-Prada et al. · 2026 · bioRxiv · Pas encore résumé

   Résumé scientifique

   The microbiome is an important regulator of metabolism and health, yet the mechanisms by which microbial communities influence host physiological state remain incompletely understood. Here we used a defined host-microbiota model consisting of Caenorhabditis elegans and an 11-member bacterial consortium representative of its natural microbiota (DefNatMta). We investigated how this native microbial community influences host metabolism and physiology relative to the standard laboratory diet, E. coli OP50. Transcriptomic analyses revealed remodelling of host pathways associated with lipid metabolism, immunity and xenobiotic detoxification. Comparison with fasting-responsive transcriptional progr…

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   Microbial cues and T cell immunity: deciphering their interactions in chronic liver disease.

   Yi-Nuo Liu, Bai-Chao Yu, Qiao-Yan Liu et al. · 2026 · Experimental and Molecular Medicine · Pas encore résumé

   Résumé scientifique

   Chronic liver disease (CLD) poses a major global health challenge, as its progression to cirrhosis and hepatocellular carcinoma significantly contributes to worldwide morbidity and mortality. Mounting evidence has identified the gut microbiota as a critical modulator of CLD progression, primarily via the gut-liver axis. The liver is continuously exposed to gut-derived signals through the portal circulation, while reciprocally secreting bioactive mediators that shape intestinal microbial composition and function. This bidirectional network enables intricate crosstalk between the gut microbiota and the host immune system. In particular, T lymphocytes, the central effectors of adaptive immunity…