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

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

Journal article

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

E Kiner, E Willie, B Vijaykumar, K Chowdhary, H Schmutz, J Chandler, A Schnell, PI Thakore, G LeGros, S Mostafavi, D Mathis, C Benoist, O Aguilar, R Allan, J Astarita, KF Austen, N Barrett, A Baysoy, BD Brown, M Buechler Show all

Nature Immunology | NATURE PORTFOLIO | Published : 2021

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 co..

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University of Melbourne Researchers

Grants

Awarded by National Institute of General Medical Sciences

Funding Acknowledgements

We thank K. Murphy, N. Yosef, V. Kuchroo, R. Ramirez, D. Ramanan, M. Sassone-Corsi, E. Pamer, A. Anderson and J. Huh for insightful discussions, data and mouse lines and K. Hattori, C. Araneo, K. Seddu, D. Dionne and the Klarman Cell Observatory team and N. El-Ali and the Bauer Core Facility for help with mice, cell sorting and single-cell profiling. This work was supported by grants from the NIH to C.B. and D.M. (AI125603) and to the ImmGen consortium (AI072073). E.K. was supported by a PhD fellowship from Boehringer Ingelheim Fonds. K.C. was supported by NIGMS-T32GM007753 and a Harvard Stem Cell Institute MD/PhD Training Fellowship.