Journal article

Gut CD4( ) T cell phenotypes are a continuum molded by microbes, not by T-H archetypes

Evgeny Kiner, Elijah Willie, Brinda Vijaykumar, Kaitavjeet Chowdhary, Hugo Schmutz, Jodie Chandler, Alexandra Schnell, Pratiksha I Thakore, Graham LeGros, Sara Mostafavi, Diane Mathis, Christophe Benoist



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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Awarded by NIH

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.