Cargando…
Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation
Treg cells are critical regulators of immune homeostasis, and environment-driven Treg cell differentiation into effector (e)Treg cells is crucial for optimal functioning. However, human Treg cell programming in inflammation is unclear. Here, we combine transcriptional and epigenetic profiling to ide...
| Autores principales: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2021
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113485/ https://www.ncbi.nlm.nih.gov/pubmed/33976194 http://dx.doi.org/10.1038/s41467-021-22975-7 |
| _version_ | 1783690870145417216 |
|---|---|
| author | Mijnheer, Gerdien Lutter, Lisanne Mokry, Michal van der Wal, Marlot Scholman, Rianne Fleskens, Veerle Pandit, Aridaman Tao, Weiyang Wekking, Mark Vervoort, Stephin Roberts, Ceri Petrelli, Alessandra Peeters, Janneke G. C. Knijff, Marthe de Roock, Sytze Vastert, Sebastiaan Taams, Leonie S. van Loosdregt, Jorg van Wijk, Femke |
| author_facet | Mijnheer, Gerdien Lutter, Lisanne Mokry, Michal van der Wal, Marlot Scholman, Rianne Fleskens, Veerle Pandit, Aridaman Tao, Weiyang Wekking, Mark Vervoort, Stephin Roberts, Ceri Petrelli, Alessandra Peeters, Janneke G. C. Knijff, Marthe de Roock, Sytze Vastert, Sebastiaan Taams, Leonie S. van Loosdregt, Jorg van Wijk, Femke |
| author_sort | Mijnheer, Gerdien |
| collection | PubMed |
| description | Treg cells are critical regulators of immune homeostasis, and environment-driven Treg cell differentiation into effector (e)Treg cells is crucial for optimal functioning. However, human Treg cell programming in inflammation is unclear. Here, we combine transcriptional and epigenetic profiling to identify a human eTreg cell signature. Inflammation-derived functional Treg cells have a transcriptional profile characterized by upregulation of both a core Treg cell (FOXP3, CTLA4, TIGIT) and effector program (GITR, BLIMP-1, BATF). We identify a specific human eTreg cell signature that includes the vitamin D receptor (VDR) as a predicted regulator in eTreg cell differentiation. H3K27ac/H3K4me1 occupancy indicates an altered (super-)enhancer landscape, including enrichment of the VDR and BATF binding motifs. The Treg cell profile has striking overlap with tumor-infiltrating Treg cells. Our data demonstrate that human inflammation-derived Treg cells acquire a conserved and specific eTreg cell profile guided by epigenetic changes, and fine-tuned by environment-specific adaptations. |
| format | Online Article Text |
| id | pubmed-8113485 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-81134852021-05-14 Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation Mijnheer, Gerdien Lutter, Lisanne Mokry, Michal van der Wal, Marlot Scholman, Rianne Fleskens, Veerle Pandit, Aridaman Tao, Weiyang Wekking, Mark Vervoort, Stephin Roberts, Ceri Petrelli, Alessandra Peeters, Janneke G. C. Knijff, Marthe de Roock, Sytze Vastert, Sebastiaan Taams, Leonie S. van Loosdregt, Jorg van Wijk, Femke Nat Commun Article Treg cells are critical regulators of immune homeostasis, and environment-driven Treg cell differentiation into effector (e)Treg cells is crucial for optimal functioning. However, human Treg cell programming in inflammation is unclear. Here, we combine transcriptional and epigenetic profiling to identify a human eTreg cell signature. Inflammation-derived functional Treg cells have a transcriptional profile characterized by upregulation of both a core Treg cell (FOXP3, CTLA4, TIGIT) and effector program (GITR, BLIMP-1, BATF). We identify a specific human eTreg cell signature that includes the vitamin D receptor (VDR) as a predicted regulator in eTreg cell differentiation. H3K27ac/H3K4me1 occupancy indicates an altered (super-)enhancer landscape, including enrichment of the VDR and BATF binding motifs. The Treg cell profile has striking overlap with tumor-infiltrating Treg cells. Our data demonstrate that human inflammation-derived Treg cells acquire a conserved and specific eTreg cell profile guided by epigenetic changes, and fine-tuned by environment-specific adaptations. Nature Publishing Group UK 2021-05-11 /pmc/articles/PMC8113485/ /pubmed/33976194 http://dx.doi.org/10.1038/s41467-021-22975-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Mijnheer, Gerdien Lutter, Lisanne Mokry, Michal van der Wal, Marlot Scholman, Rianne Fleskens, Veerle Pandit, Aridaman Tao, Weiyang Wekking, Mark Vervoort, Stephin Roberts, Ceri Petrelli, Alessandra Peeters, Janneke G. C. Knijff, Marthe de Roock, Sytze Vastert, Sebastiaan Taams, Leonie S. van Loosdregt, Jorg van Wijk, Femke Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation |
| title | Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation |
| title_full | Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation |
| title_fullStr | Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation |
| title_full_unstemmed | Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation |
| title_short | Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation |
| title_sort | conserved human effector treg cell transcriptomic and epigenetic signature in arthritic joint inflammation |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113485/ https://www.ncbi.nlm.nih.gov/pubmed/33976194 http://dx.doi.org/10.1038/s41467-021-22975-7 |
| work_keys_str_mv | AT mijnheergerdien conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT lutterlisanne conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT mokrymichal conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT vanderwalmarlot conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT scholmanrianne conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT fleskensveerle conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT panditaridaman conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT taoweiyang conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT wekkingmark conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT vervoortstephin conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT robertsceri conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT petrellialessandra conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT peetersjannekegc conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT knijffmarthe conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT deroocksytze conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT vastertsebastiaan conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT taamsleonies conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT vanloosdregtjorg conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation AT vanwijkfemke conservedhumaneffectortregcelltranscriptomicandepigeneticsignatureinarthriticjointinflammation |