Nature immunology, 2021-02, Vol.22 (2), p.216
2021
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Details
- Autor(en) / Beteiligte
- Titel
- Gut CD4 + T cell phenotypes are a continuum molded by microbes, not by T H archetypes
- Ist Teil von
- Nature immunology, 2021-02, Vol.22 (2), p.216
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- CD4 effector lymphocytes (T ) are traditionally classified by the cytokines they produce. To determine the states that T cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic T 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 (T ) subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as T markers were distributed in a polarized continuum, which was functionally validated. Clones derived from single progenitors gave rise to both IFN-γ- 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 RORγ.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1529-2916DOI: 10.1038/s41590-020-00836-7Titel-ID: cdi_pubmed_primary_33462454
- Format
- –
- Schlagworte
- Animals, Bacteria - immunology, Bacteria - pathogenicity, Bacterial Infections - genetics, Bacterial Infections - immunology, Bacterial Infections - metabolism, Bacterial Infections - microbiology, CD4-Positive T-Lymphocytes - immunology, CD4-Positive T-Lymphocytes - metabolism, CD4-Positive T-Lymphocytes - microbiology, CD4-Positive T-Lymphocytes - parasitology, Chromatin - genetics, Chromatin - metabolism, Citrobacter rodentium - immunology, Citrobacter rodentium - pathogenicity, Colon - immunology, Colon - metabolism, Colon - microbiology, Colon - parasitology, Cytokines - genetics, Cytokines - metabolism, Disease Models, Animal, Gastrointestinal Microbiome, Gene Expression Profiling, Heligmosomatoidea - immunology, Heligmosomatoidea - pathogenicity, Host-Pathogen Interactions, Interferon Regulatory Factors - genetics, Interferon Regulatory Factors - metabolism, Intestinal Diseases, Parasitic - genetics, Intestinal Diseases, Parasitic - immunology, Intestinal Diseases, Parasitic - metabolism, Intestinal Diseases, Parasitic - parasitology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nematospiroides dubius - immunology, Nematospiroides dubius - pathogenicity, Nippostrongylus - immunology, Nippostrongylus - pathogenicity, Phenotype, Salmonella enterica - immunology, Salmonella enterica - pathogenicity, Single-Cell Analysis, Transcription Factor AP-1 - genetics, Transcription Factor AP-1 - metabolism, Transcriptome