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
NATURE IMMUNOLOGY | NATURE RESEARCH | Published : 2021
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..View full abstract
Awarded by NIH
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.