| First Author | Kiner E | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 2 | Pages | 216-228 |
| PubMed ID | 33462454 | Mgi Jnum | J:336889 |
| Mgi Id | MGI:6706659 | Doi | 10.1038/s41590-020-00836-7 |
| Citation | Kiner E, et al. (2021) Gut CD4(+) T cell phenotypes are a continuum molded by microbes, not by TH archetypes. Nat Immunol 22(2):216-228 |
| abstractText | 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-gamma- 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 RORgamma. |
