Terminal differentiation and persistence of effector regulatory T cells essential for preventing intestinal inflammation
Regulatory T (T<sub>reg</sub>) cells are a specialized CD4<sup>+</sup> T cell lineage with essential anti-inflammatory functions. Analysis of T<sub>reg</sub> cell adaptations to non-lymphoid tissues that enable their specialized immunosuppressive and tissue-supportive functions raises questions about the underlying mechanisms of these adaptations and whether they represent stable differentiation or reversible activation states. Here, we characterize distinct colonic effector T<sub>reg</sub> cell transcriptional programs. Attenuated T cell receptor (TCR) signaling and acquisition of substantial TCR-independent functionality seems to facilitate the terminal differentiation of a population of colonic effector T<sub>reg</sub> cells that are distinguished by stable expression of the immunomodulatory cytokine IL-10. Functional studies show that this subset of effector T<sub>reg</sub> cells, but not their expression of IL-10, is indispensable for colonic health. These findings identify core features of the terminal differentiation of effector T<sub>reg</sub> cells in non-lymphoid tissues and their function.
Authors
- Ariella Glasner (ORCID: https://orcid.org/0000-0001-7122-881X)
- Andrew G. Levine (ORCID: https://orcid.org/0000-0003-3717-7558)
- Alexander Y. Rudensky (ORCID: https://orcid.org/0000-0003-1280-2898)
- Chirag Krishna (ORCID: https://orcid.org/0000-0002-9166-4632)
- Zhong-Min Wang
- Stanislav Dikiy (ORCID: https://orcid.org/0000-0002-8287-6561)
- Aazam P. Ghelani
- Benjamin D. Greenbaum (ORCID: https://orcid.org/0000-0001-6153-8793)
- Yuri Pritykin
- Paolo Giovanelli (ORCID: https://orcid.org/0000-0002-5799-6721)
- Giorgi Beroshvili (ORCID: https://orcid.org/0000-0002-8038-1493)
- Christina S. Leslie (ORCID: https://orcid.org/0000-0002-4571-5910)
- Stephen Martis (ORCID: https://orcid.org/0000-0003-1735-2347)
- Xiao Jun Huang (ORCID: https://orcid.org/0000-0003-1906-5819)
Institutions
- Scripps Research Institute (US)
- Scripps Health (US)
- Memorial Sloan Kettering Cancer Center (US)
- Howard Hughes Medical Institute (US)
- University of California, San Francisco (US)
- Princeton University (US)
- Cornell University (US)
- Swim Across America (US)
Publication Details
- Journal
- Nature Immunology
- Published
- 2025-02-04
- DOI
- https://doi.org/10.1038/s41590-024-02075-6
- Citations
- 15
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 11.96
Funders
- Howard Hughes Medical Institute
- Memorial Sloan-Kettering Cancer Center
- Ludwig Institute for Cancer Research
- National Institutes of Health
- Ludwig Center at Harvard
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases