The intestinal microbiota plays a key role in host metabolism, immune system development and protection against pathogens. It can also elicit immunopathology leading to inflammatory bowel diseases. The group is interested in MAIT cell responses against microbiota-derived ligands.

The distinctive feature of MAIT cells, which is conserved across evolution, is their unique specificity for small metabolites derived from the riboflavin biosynthetic pathway, found in most bacteria but absent in animals. MAIT cells are lacking in germ-free mice, and we found that MAIT cell development relies on the transfer of microbiota-derived ligands from the gut to the thymus. The determinants of MAIT ligand production in vivo are unknown. After thymic egress, MAIT cells populate mucosal tissues such as the gut (where they represent 1-10% of T cells in humans) and liver (10-45% of T cells), yet the function of MAIT cells in these tissue sites remains elusive.

We use gnotobiotic and genetic models, coupled to metagenomic approaches to further understand this host – microbiota interaction in vivo:

• What are the rules governing MAIT ligand synthesis by the microbiota?
• How do microbiota-derived ligands circulate in the body and shape MAIT cell populations?
• What is the role of MAIT cells in the gut? Are they beneficial or deleterious during intestinal inflammation?
• Can we develop new pre-clinical tools to manipulate MAIT cells and reduce intestinal pathology?

Salou*, Legoux*, Gilet*, Darbois, du Halgouet, Alonso, Richer, Goubet, Daviaud, Menger, Procopio, Premel, Lantz. A common transcriptomic program acquired in the thymus defines tissue-residency of MAIT and NKT subsets. Journal of Experimental Medicine (IF 14.3) 2019 216:133-151. doi: 10.1084/jem.20181483. *Co-first authors.

Legoux*#, Gilet*, Procopio, Echasserieau, Bernardeau, Lantz#. Molecular mechanisms of lineage decisions in metabolite-specific T cells. Nature immunology (IF 25.6) 2019 20: 1244-1255. doi: 10.1038/s41590-019-0465-3. *Co-first authors. #Co-corresponding authors

Legoux#, Bellet, Daviaud, El Morr, Darbois, Niort, Procopio, Salou, Gilet, Ryffel, Balvay, Foussier, Sarkis, El Marjou, Schmidt, Rabot and Lantz#. Microbial metabolites control thymic development of Mucosal Associated Invariant T cells. Science (IF 47.7) 2019 366: 494-499. doi: 10.1126/science.aaw2719. #Co-corresponding authors. Comments in Science. 2019 Oct 25;366(6464):419-420; Nat Rev Immunol. 2019 Nov;19(11):662-663; Cardiovasc Res. 2020 Feb 1;116(2):e21-e22

Legoux*, Salou*, Lantz. MAIT cell development and function: the microbial connection. Immunity (IF 31.7) 2020 4:710. doi: 10.1016/j.immuni.2020.09.009. Review. *Co-first authors.

Zhang*, Legoux*, Vaughan, Moon. Opposing peripheral fates of tissue-restricted self-antigen-specific conventional and regulatory CD4+ T cells. European Journal of Immunology (IF 5.5) 2020. 50: 63-72. doi: 10.1002/eji.201948180. *Co-first authors.

Salou*, Legoux*, Lantz. MAIT cell development in mice and humans. Molecular Immunology (IF 4.4) 2021 130:31. doi: 10.1016/j.molimm.2020.12.003. Review. *Equal contribution.

Bugaut*, El Morr*, Mestdagh, Darbois, Paiva, Salou, Perrin, Fürstenheim, du Halgouet, Bilonda-Mutala, Le Gac, Arnaud, El Marjou, Guerin, Chaiyasitdhi, Piquet, Smadja, Cieslak, Ryffel, Maciulyte, Turner, Bernardeau, Montagutelli, Lantz# and Legoux#. A conserved transcriptional program for MAIT cells across mammalian evolution. Journal of Experimental Medicine (IF 14.3) 2024 221:2 doi: 10.1084/jem.20231487. *Co-first authors #Co-corresponding authors.

El Morr*, Fürhensteim*, Mestdagh, Franciskiewicz, Salou, Morvan, Dupré, Vorobev, Jneid, Premel, Darbois, Perrin, Mondot, Colombau, Bugaut, du Halgouet, Richon, Procopiot, Maurin, Phillippe, Rodriguez, Lantz# and Legoux#. MAIT cells monitor intestinal dysbiosis and contribute to host protection during colitis. Science Immunology (IF 16.3) 2024. 9:86 doi: 10.1126/sciimunol.adi8954 *Co-first authors. #Co-corresponding authors.

Germain, Veloso, Lantz and Legoux. Journal of Experimental Medicine (IF 14.3) 2025 222:1 doi: 10.1084/jem.20232298. Review.