학술논문

Gut CD4+T cell phenotypes are a continuum molded by microbes, not by THarchetypes
Document Type
Article
Source
Nature Immunology; February 2021, Vol. 22 Issue: 2 p216-228, 13p
Subject
Language
ISSN
15292908; 15292916
Abstract
CD4+effector lymphocytes (Teff) are traditionally classified by the cytokines they produce. To determine the states that Teffcells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic Teffcells 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 THmarkers were distributed in a polarized continuum, which was functionally validated. Clones derived from single progenitors gave rise to both IFN-?- 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 ROR?.