TY - JOUR
T1 - Thymic development of gut-microbiota-specific T cells
AU - Zegarra-Ruiz, Daniel F.
AU - Kim, Dasom V.
AU - Norwood, Kendra
AU - Kim, Myunghoo
AU - Wu, Wan Jung H.
AU - Saldana-Morales, Fatima B.
AU - Hill, Andrea A.
AU - Majumdar, Shubhabrata
AU - Orozco, Stephanie
AU - Bell, Rickesha
AU - Round, June L.
AU - Longman, Randy S.
AU - Egawa, Takeshi
AU - Bettini, Matthew L.
AU - Diehl, Gretchen E.
N1 - Funding Information:
Acknowledgements This work was supported by NIH grants R01AI136963 (G.E.D. and M.L.B.), R01AI125264 (G.E.D.), R01DK114456 (M.L.B.), R01AI130152 (T.E.) and R01 DK114252 (R.S.L.); the Kleberg Foundation (G.E.D. and M.L.B); the Kenneth Rainin Foundation (G.E.D.); the Leukemia and Lymphoma Society Scholar Award (T.E.); and the Cytometry and Cell Sorting Core at Baylor College of Medicine, with funding from the CPRIT Core Facility Support Award (CPRIT-RP180672) and the NIH (P30 CA125123 and S10 RR024574) and with the assistance of J. M. Sederstrom. We thank the Baylor College of Medicine Genetically Engineered Mouse Core supported by the Cancer Center Grant (P30 CA125123); the Mouse Embryonic Stem Cell Core at Baylor College of Medicine; D. Littman and C.-S. Hsieh for critical reading of the manuscript; N. Ajami for advice on 16S; and the NIH Tetramer Facility, which is supported by contract HHSN272201300006C from the NIAID.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/6/17
Y1 - 2021/6/17
N2 - Humans and their microbiota have coevolved a mutually beneficial relationship in which the human host provides a hospitable environment for the microorganisms and the microbiota provides many advantages for the host, including nutritional benefits and protection from pathogen infection1. Maintaining this relationship requires a careful immune balance to contain commensal microorganisms within the lumen while limiting inflammatory anti-commensal responses1,2. Antigen-specific recognition of intestinal microorganisms by T cells has previously been described3,4. Although the local environment shapes the differentiation of effector cells3–5 it is unclear how microbiota-specific T cells are educated in the thymus. Here we show that intestinal colonization in early life leads to the trafficking of microbial antigens from the intestine to the thymus by intestinal dendritic cells, which then induce the expansion of microbiota-specific T cells. Once in the periphery, microbiota-specific T cells have pathogenic potential or can protect against related pathogens. In this way, the developing microbiota shapes and expands the thymic and peripheral T cell repertoire, allowing for enhanced recognition of intestinal microorganisms and pathogens.
AB - Humans and their microbiota have coevolved a mutually beneficial relationship in which the human host provides a hospitable environment for the microorganisms and the microbiota provides many advantages for the host, including nutritional benefits and protection from pathogen infection1. Maintaining this relationship requires a careful immune balance to contain commensal microorganisms within the lumen while limiting inflammatory anti-commensal responses1,2. Antigen-specific recognition of intestinal microorganisms by T cells has previously been described3,4. Although the local environment shapes the differentiation of effector cells3–5 it is unclear how microbiota-specific T cells are educated in the thymus. Here we show that intestinal colonization in early life leads to the trafficking of microbial antigens from the intestine to the thymus by intestinal dendritic cells, which then induce the expansion of microbiota-specific T cells. Once in the periphery, microbiota-specific T cells have pathogenic potential or can protect against related pathogens. In this way, the developing microbiota shapes and expands the thymic and peripheral T cell repertoire, allowing for enhanced recognition of intestinal microorganisms and pathogens.
UR - http://www.scopus.com/inward/record.url?scp=85105773604&partnerID=8YFLogxK
U2 - 10.1038/s41586-021-03531-1
DO - 10.1038/s41586-021-03531-1
M3 - Article
C2 - 33981034
AN - SCOPUS:85105773604
VL - 594
SP - 413
EP - 417
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7863
ER -