Commensal epitopes drive differentiation of colonic T-regs

Kuczma, Michal P.; Szurek, Edyta A.; Cebula, Anna; Chassaing, Benoit; Jung, Yu-Jin; Kang, Sang-Moo; Fox, James G.; Stecher, Baerbel und Ignatowicz, Leszek (2020): Commensal epitopes drive differentiation of colonic T-regs. In: Science Advances, Bd. 6, Nr. 16, eaaz3186

Abstract

The gut microbiome is the largest source of intrinsic non-self-antigens that are continuously sensed by the immune system but typically do not elicit lymphocyte responses. CD4(+) T cells are critical to sustain uninterrupted tolerance to microbial antigens and to prevent intestinal inflammation. However, clinical interventions targeting commensal bacteria-specific CD4(+) T cells are rare, because only a very limited number of commensal-derived epitopes have been identified. Here, we used a new approach to study epitopes and identify T cell receptors expressed by CD4(+)Foxp3(+) (T-reg) cells specific for commensal-derived antigens. Using this approach, we found that antigens from Akkermansia muciniphila reprogram naive CD4(+) T cells to the T-reg lineage, expand preexisting microbe specific T-regs, and limit wasting disease in the CD4(+) T cell transfer model of colitis. These data suggest that the administration of specific commensal epitopes may help to widen the repertoire of specific T-regs that control intestinal inflammation.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2375-2548
• Sprache: Englisch