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1811074989685735424
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| collection |
MIT
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| description |
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. + eff eff eff H H
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| first_indexed |
2024-09-23T09:58:37Z
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| format |
Article
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| id |
mit-1721.1/135272
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| institution |
Massachusetts Institute of Technology
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| language |
English
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| last_indexed |
2024-09-23T09:58:37Z
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| publishDate |
2021
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| publisher |
Springer Science and Business Media LLC
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| record_format |
dspace
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| spelling |
mit-1721.1/1352722022-04-01T17:27:48Z Gut CD4<sup>+</sup> T cell phenotypes are a continuum molded by microbes, not by T<inf>H</inf> archetypes 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. + eff eff eff H H 2021-10-27T20:22:43Z 2021-10-27T20:22:43Z 2021-02-01 2021-07-22T17:54:38Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135272 en 10.1038/s41590-020-00836-7 Nature Immunology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Science and Business Media LLC PMC
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| spellingShingle |
Gut CD4<sup>+</sup> T cell phenotypes are a continuum molded by microbes, not by T<inf>H</inf> archetypes
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| title |
Gut CD4<sup>+</sup> T cell phenotypes are a continuum molded by microbes, not by T<inf>H</inf> archetypes
|
| title_full |
Gut CD4<sup>+</sup> T cell phenotypes are a continuum molded by microbes, not by T<inf>H</inf> archetypes
|
| title_fullStr |
Gut CD4<sup>+</sup> T cell phenotypes are a continuum molded by microbes, not by T<inf>H</inf> archetypes
|
| title_full_unstemmed |
Gut CD4<sup>+</sup> T cell phenotypes are a continuum molded by microbes, not by T<inf>H</inf> archetypes
|
| title_short |
Gut CD4<sup>+</sup> T cell phenotypes are a continuum molded by microbes, not by T<inf>H</inf> archetypes
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| title_sort |
gut cd4 sup sup t cell phenotypes are a continuum molded by microbes not by t inf h inf archetypes
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| url |
https://hdl.handle.net/1721.1/135272
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