Commensal epitopes drive differentiation of colonic T regs
© 2020 The Authors. 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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2021
|
| Online Access: | https://hdl.handle.net/1721.1/135693 |
| _version_ | 1811081248976666624 |
|---|---|
| author | Kuczma, Michal P Szurek, Edyta A Cebula, Anna Chassaing, Benoit Jung, Yu-Jin Kang, Sang-Moo Fox, James G Stecher, Bärbel Ignatowicz, Leszek |
| author_facet | Kuczma, Michal P Szurek, Edyta A Cebula, Anna Chassaing, Benoit Jung, Yu-Jin Kang, Sang-Moo Fox, James G Stecher, Bärbel Ignatowicz, Leszek |
| author_sort | Kuczma, Michal P |
| collection | MIT |
| description | © 2020 The Authors. 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+ (Treg) cells specific for commensal-derived antigens. Using this approach, we found that antigens from Akkermansia muciniphila reprogram naïve CD4+ T cells to the Treg lineage, expand preexisting microbe specific Tregs, 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 Tregs that control intestinal inflammation. |
| first_indexed | 2024-09-23T11:43:45Z |
| format | Article |
| id | mit-1721.1/135693 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:43:45Z |
| publishDate | 2021 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1356932021-10-28T04:12:17Z 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, Bärbel Ignatowicz, Leszek © 2020 The Authors. 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+ (Treg) cells specific for commensal-derived antigens. Using this approach, we found that antigens from Akkermansia muciniphila reprogram naïve CD4+ T cells to the Treg lineage, expand preexisting microbe specific Tregs, 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 Tregs that control intestinal inflammation. 2021-10-27T20:28:50Z 2021-10-27T20:28:50Z 2020 2021-09-13T13:52:36Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135693 en 10.1126/SCIADV.AAZ3186 Science Advances Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/3.0/ application/pdf American Association for the Advancement of Science (AAAS) Science Advances |
| spellingShingle | Kuczma, Michal P Szurek, Edyta A Cebula, Anna Chassaing, Benoit Jung, Yu-Jin Kang, Sang-Moo Fox, James G Stecher, Bärbel Ignatowicz, Leszek Commensal epitopes drive differentiation of colonic T regs |
| title | Commensal epitopes drive differentiation of colonic T regs |
| title_full | Commensal epitopes drive differentiation of colonic T regs |
| title_fullStr | Commensal epitopes drive differentiation of colonic T regs |
| title_full_unstemmed | Commensal epitopes drive differentiation of colonic T regs |
| title_short | Commensal epitopes drive differentiation of colonic T regs |
| title_sort | commensal epitopes drive differentiation of colonic t regs |
| url | https://hdl.handle.net/1721.1/135693 |
| work_keys_str_mv | AT kuczmamichalp commensalepitopesdrivedifferentiationofcolonictregs AT szurekedytaa commensalepitopesdrivedifferentiationofcolonictregs AT cebulaanna commensalepitopesdrivedifferentiationofcolonictregs AT chassaingbenoit commensalepitopesdrivedifferentiationofcolonictregs AT jungyujin commensalepitopesdrivedifferentiationofcolonictregs AT kangsangmoo commensalepitopesdrivedifferentiationofcolonictregs AT foxjamesg commensalepitopesdrivedifferentiationofcolonictregs AT stecherbarbel commensalepitopesdrivedifferentiationofcolonictregs AT ignatowiczleszek commensalepitopesdrivedifferentiationofcolonictregs |