Biology subjects

Gelineau, A.

Publications and source records attributed to Gelineau, A..

2 recordsLinked to original sources

bioRxiv2025

Decoding Peripheral Tolerance: TCR Rules for pTreg differentiation in the Gut

Peripheral differentiation of regulatory T cells (pTregs) promoted by foreign antigens encountered in barrier tissues is considered a unique contributor to immunological tolerance to obligate non-self, like food or symbiotic microbes. The relative importance of adaptive recognition via the T cell receptor (TCR) vs environmental small-molecule or neuroimmune cues, is poorly understood. We leverage CRISPR-based TCR editing to perform in primary T cells in vivo, with a large panel of TCRs, a screen to assess pTreg differentiation induced by self, microbial, or dietary antigens. All antigen classes drive pTreg differentiation, which varies with the origin of the TCR: TCRs derived from Tregs enable pTreg differentiation much more effectively than those from Tconv. TCRs recognizing self, microbial, or dietary antigens elicit distinct pTreg phenotypes, Helios, ROR{gamma}, or both. Mechanistically, these trace to different types of antigen-presenting-cell involved. That Treg-derived TCRs preferentially drive tolerogenic fate speaks to preferential drivers of tolerogenic therapy.

immunology↗

bioRxiv2023

Dietary fibers benefits on glucose homeostasis require type 2 conventional dendritic cells in mice fed a high-fat diet

Diet composition impacts metabolic health and is now recognized to shape the immune system, especially in the intestinal tract. Nutritional imbalance and increased caloric intake are induced by high-fat diet (HFD) in which lipids are enriched at the expense of dietary fibers. Such nutritional challenge alters glucose homeostasis as well as intestinal immunity. Here, we observed that short-term HFD induced dysbiosis, glucose intolerance and decreased intestinal ROR{gamma}t+ CD4 T cells, including peripherally-induced Tregs and IL17-producing (Th17) T cells. However, dietary fiber supplementation of HFD-fed animals was sufficient to maintain ROR{gamma}t+ CD4 T cell subsets and microbial species known to induce them, alongside having a beneficial impact on glucose tolerance. Dietary fiber-mediated normalization of Th17 cells and amelioration of glucose handling required the cDC2 dendritic cell subset in HFD-fed animals, while IL-17 neutralization limited fibers impact on glucose tolerance. Overall, we uncover a novel and pivotal role of cDC2 in the control of the immune and metabolic effects of dietary fibers in the context of HFD feeding.

immunology↗