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Thymic development of gut-microbiota-specific T cells.

TitleThymic development of gut-microbiota-specific T cells.
Publication TypeJournal Article
Year of Publication2021
AuthorsZegarra-Ruiz DF, Kim DV, Norwood K, Kim M, Wu W-JH, Saldana-Morales FB, Hill AA, Majumdar S, Orozco S, Bell R, Round JL, Longman RS, Egawa T, Bettini ML, Diehl GE
JournalNature
Volume594
Issue7863
Pagination413-417
Date Published2021 06
ISSN1476-4687
KeywordsAging, Animals, Antigens, Bacterial, CX3C Chemokine Receptor 1, Dendritic Cells, DNA, Bacterial, Escherichia coli, Female, Gastrointestinal Microbiome, Male, Mice, Organ Specificity, Salmonella, Symbiosis, T-Lymphocytes, Thymus Gland
Abstract

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.

DOI10.1038/s41586-021-03531-1
Alternate JournalNature
PubMed ID33981034
PubMed Central IDPMC8323488
Grant ListR01 AI136963 / AI / NIAID NIH HHS / United States
HHSN272201300006C / AI / NIAID NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States
S10 RR024574 / RR / NCRR NIH HHS / United States
R01 AI125264 / AI / NIAID NIH HHS / United States
R01 DK114456 / DK / NIDDK NIH HHS / United States
R01 DK114252 / DK / NIDDK NIH HHS / United States
R01 AI130152 / AI / NIAID NIH HHS / United States