Kiner, E;
Willie, E;
Vijaykumar, B;
Chowdhary, K;
Schmutz, H;
Chandler, J;
Schnell, A;
... Yoshida, H; + view all
(2021)
Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes.
Nature Immunology
, 22
pp. 216-228.
10.1038/s41590-020-00836-7.
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Abstract
CD4+ effector lymphocytes (Teff) are traditionally classified by the cytokines they produce. To determine the states that Teff cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic Teff 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 (TH) subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as TH 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.
| Type: | Article |
|---|---|
| Title: | Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41590-020-00836-7 |
| Publisher version: | http://dx.doi.org/10.1038/s41590-020-00836-7 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Animals, Bacteria, Bacterial Infections, CD4-Positive T-Lymphocytes, Chromatin, Citrobacter rodentium, Colon, Cytokines, Disease Models, Animal, Gastrointestinal Microbiome, Gene Expression Profiling, Heligmosomatoidea, Host-Pathogen Interactions, Interferon Regulatory Factors, Intestinal Diseases, Parasitic, Male, Mice, Inbred C57BL, Mice, Transgenic, Nematospiroides dubius, Nippostrongylus, Phenotype, Salmonella enterica, Single-Cell Analysis, Transcription Factor AP-1, Transcriptome, Mice |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10189148 |
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