Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes

Kiner E, Willie E, Schmutz H, Chandler J, Schnell A, Thakore PI, LeGros G, Mostafavi S, Benoist C, Aguilar O, Allan R, Astarita J, Austen KF, Barrett N, Baysoy A, Brown BD, Buechler M, Buenrostro J, Casanova MA, Choi K, Chowdhary K, Colonna M, Crowl T, Deng T, Desai JV, Desland F, Dhainaut M, Ding J, Dominguez C, Dwyer D, Frascoli M, Gal-Oz S, Goldrath A, Grieshaber-Bouyer R, Jia B, Johanson T, Jordan S, Kang J, Kapoor V, Kenigsberg E, Kim J, wook Kim K, Kronenberg M, Lanier L, Laplace C, Lareau C, Leader A, Lee J, Magen A, Maier B, Maslova A, Mathis D, McFarland A, Merad M, Meunier E, Monach P, Muller S, Muus C, Ner-Gaon H, Nguyen Q, Nigrovic PA, Novakovsky G, Nutt S, Omilusik K, Ortiz-Lopez A, Paynich M, Peng V, Potempa M, Pradhan R, Quon S, Ramirez R, Ramanan D, Randolph G, Regev A, Rose SA, Seddu K, Shay T, Shemesh A, Shyer J, Smilie C, Spidale N, Subramanian A, Sylvia K, Tellier J, Turley S, Vijaykumar B, Wagers A, Wang C, Wang PL, Wroblewska A, Yang L, Yim A, Yoshida H (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 22

Pages Range: 216-228

Journal Issue: 2

DOI: 10.1038/s41590-020-00836-7

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.

Authors with CRIS profile

Involved external institutions

Harvard University United States (USA) (US) University of British Columbia Canada (CA) Malaghan Institute of Medical Research New Zealand (NZ) Brigham and Women's Hospital (BWH) United States (USA) (US) Eli and Edythe L. Broad Institute of MIT and Harvard United States (USA) (US) Malaghan Institute of Medical Research New Zealand (NZ) University of California San Francisco (UCSF) United States (USA) (US) Walter and Eliza Hall Institute of Medical Research (WEHI) Australia (AU) Genentech Inc. United States (USA) (US) Icahn School of Medicine at Mount Sinai United States (USA) (US) Washington University in St. Louis United States (USA) (US) University of California, San Diego (UC San Diego, UCSD) United States (USA) (US) National Institute of Allergy and Infectious Diseases United States (USA) (US) Icahn School of Medicine at Mount Sinai United States (USA) (US) University of Massachusetts Medical School United States (USA) (US) Ben-Gurion University of the Negev (BGU) / אוניברסיטת בן-גוריון בנגב Israel (IL) University of British Columbia Canada (CA) Brigham and Women's Hospital (BWH) United States (USA) (US) Walter and Eliza Hall Institute of Medical Research (WEHI) Australia (AU) Harvard University United States (USA) (US) University of Massachusetts Medical School United States (USA) (US) University of California, San Diego (UC San Diego, UCSD) United States (USA) (US) Genentech Inc. United States (USA) (US) Ben-Gurion University of the Negev (BGU) / אוניברסיטת בן-גוריון בנגב Israel (IL) IMS RIKEN Center for Integrative Medical Sciences Japan (JP)

How to cite

APA:

Kiner, E., Willie, E., Schmutz, H., Chandler, J., Schnell, A., Thakore, P.I.,... Yoshida, H. (2021). Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes. Nature Immunology, 22(2), 216-228. https://doi.org/10.1038/s41590-020-00836-7

MLA:

Kiner, Evgeny, et al. "Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes." Nature Immunology 22.2 (2021): 216-228.

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