Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes
Name
nihms-1644905.pdf
Description
Accepted version
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2.65 MB
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Checksum (MD5)
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Author(s)
Kiner, Evgeny
Willie, Elijah
Vijaykumar, Brinda
Chowdhary, Kaitavjeet
Schmutz, Hugo
Chandler, Jodie
Schnell, Alexandra
Thakore, Pratiksha I.
LeGros, Graham
Mostafavi, Sara
Date Issued
January 2021
Journal
Nature Immunology
Publisher
Springer Science and Business Media LLC
Version
Author's final manuscript
Abstract
CD4 effector lymphocytes (T ) are traditionally classified by the cytokines they produce. To determine the states that T cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic T cells in germ-free or conventional mice or in mice after challenge with a range of phenotypically biasing microbes. Unexpected subsets were marked by the expression of the interferon (IFN) signature or myeloid-specific transcripts, but transcriptome or chromatin structure could not resolve discrete clusters fitting classic helper T cell (T ) subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as T markers were distributed in a polarized continuum, which was functionally validated. Clones derived from single progenitors gave rise to both IFN-γ- and interleukin (IL)-17-producing cells. Most of the transcriptional variance was tied to the infecting agent, independent of the cytokines produced, and chromatin variance primarily reflected activities of activator protein (AP)-1 and IFN-regulatory factor (IRF) transcription factor (TF) families, not the canonical subset master regulators T-bet, GATA3 or RORγ. + eff eff eff H H
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/s41590-020-00836-7
