| Title: |
Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes |
| Authors: |
Kiner, E; Willie, E; Vijaykumar, B; Chowdhary, K; Schmutz, H; Chandler, J; Schnell, A; Thakore, PI; LeGros, G; Mostafavi, S; Mathis, D; Benoist, C; Aguilar, O; Allan, R; Astarita, J; Austen, KF; Barrett, N; Baysoy, A; Brown, BD; Buechler, M; Buenrostro, J; Casanova, MA; Choi, K; Colonna, M; Crowl, T; Deng, T; Desai, JV; Desland, F; Dhainaut, M; Ding, J; Dominguez, C; Dwyer, D; Frascoli, M; Gal-Oz, S; Goldrath, A; Grieshaber-Bouyer, R; Jia, B; Johanson, T; Jordan, S; Kang, J; Kapoor, V; Kenigsberg, E; Kim, J; wook Kim, K; Kronenberg, M; Lanier, L; Laplace, C; Lareau, C; Leader, A; Lee, J; Magen, A; Maier, B; Maslova, A; McFarland, A; Merad, M; Meunier, E; Monach, P; Muller, S; Muus, C; Ner-Gaon, H; Nguyen, Q; Nigrovic, PA; Novakovsky, G; Nutt, S; Omilusik, K; Ortiz-Lopez, A; Paynich, M; Peng, V; Potempa, M; Pradhan, R; Quon, S; Ramirez, R; Ramanan, D; Randolph, G; Regev, A; Rose, SA; Seddu, K; Shay, T; Shemesh, A; Shyer, J; Smilie, C; Spidale, N; Subramanian, A; Sylvia, K; Tellier, J; Turley, S; Wagers, A; Wang, C; Wang, PL; Wroblewska, A; Yang, L; Yim, A; Yoshida, H |
| Source: |
Nature Immunology , 22 pp. 216-228. (2021) |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2021 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Animals; Bacteria; Bacterial Infections; CD4-Positive T-Lymphocytes; Chromatin; Citrobacter rodentium; Colon; Cytokines; Disease Models; Animal; Gastrointestinal Microbiome; Gene Expression Profiling; Heligmosomatoidea; Host-Pathogen Interactions; Interferon Regulatory Factors; Intestinal Diseases; Parasitic; Male; Mice; Inbred C57BL; Transgenic; Nematospiroides dubius; Nippostrongylus; Phenotype; Salmonella enterica; Single-Cell Analysis; Transcription Factor AP-1; Transcriptome |
| Description: |
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-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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10189148/1/Gut%20CD4sup%2Bsup%20T%20cell%20phenotypes%20are%20a%20continuum%20molded%20by%20microbes,%20not%20by%20TsubHsub%20archetypes.pdf; https://discovery.ucl.ac.uk/id/eprint/10189148/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10189148/1/Gut%20CD4sup%2Bsup%20T%20cell%20phenotypes%20are%20a%20continuum%20molded%20by%20microbes,%20not%20by%20TsubHsub%20archetypes.pdf; https://discovery.ucl.ac.uk/id/eprint/10189148/ |
| Rights: |
open |
| Accession Number: |
edsbas.B38C4744 |
| Database: |
BASE |