Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity
Th17 cells are key players in defense against pathogens and maintaining tissue homeostasis, but also act as critical drivers of autoimmune diseases. Based on single-cell RNA-seq profiling of pathogenic versus nonpathogenic Th17 cells, we identified protein C receptor (PROCR) as a cell surface molecu...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Rockefeller University Press, The
2017
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| Online Access: | http://hdl.handle.net/1721.1/108596 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1811072319064375296 |
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| author | Kishi, Yasuhiro Kondo, Takaaki Xiao, Sheng Yosef, Nir Gaublomme, Jellert Wu, Chuan Wang, Chao Chihara, Norio Regev, Aviv Joller, Nicole Kuchroo, Vijay K. |
| author2 | Broad Institute of MIT and Harvard |
| author_facet | Broad Institute of MIT and Harvard Kishi, Yasuhiro Kondo, Takaaki Xiao, Sheng Yosef, Nir Gaublomme, Jellert Wu, Chuan Wang, Chao Chihara, Norio Regev, Aviv Joller, Nicole Kuchroo, Vijay K. |
| author_sort | Kishi, Yasuhiro |
| collection | MIT |
| description | Th17 cells are key players in defense against pathogens and maintaining tissue homeostasis, but also act as critical drivers of autoimmune diseases. Based on single-cell RNA-seq profiling of pathogenic versus nonpathogenic Th17 cells, we identified protein C receptor (PROCR) as a cell surface molecule expressed in covariance with the regulatory module of Th17 cells. Although PROCR expression in T cells was controlled by the cooperative action of the Th17 lineage-specific transcription factors RORγt, IRF4, and STAT3, PROCR negatively regulated Th17 differentiation. CD4+ T cells from PROCR low expressor mutant mice readily differentiated into Th17 cells, whereas addition of the PROCR ligand, activated protein C, inhibited Th17 differentiation in vitro. In addition, PROCR acted as a negative regulator of Th17 pathogenicity in that it down-regulated expression of several pathogenic signature genes, including IL-1 and IL-23 receptors. Furthermore, T cell–specific deficiency of PROCR resulted in the exacerbation of experimental autoimmune encephalomyelitis (EAE) and higher frequencies of Th17 cell in vivo, indicating that PROCR also inhibits pathogenicity of Th17 cells in vivo. PROCR thus does not globally inhibit Th17 responses but could be targeted to selectively inhibit proinflammatory Th17 cells. |
| first_indexed | 2024-09-23T09:04:05Z |
| format | Article |
| id | mit-1721.1/108596 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:04:05Z |
| publishDate | 2017 |
| publisher | Rockefeller University Press, The |
| record_format | dspace |
| spelling | mit-1721.1/1085962022-09-26T10:14:22Z Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity Kishi, Yasuhiro Kondo, Takaaki Xiao, Sheng Yosef, Nir Gaublomme, Jellert Wu, Chuan Wang, Chao Chihara, Norio Regev, Aviv Joller, Nicole Kuchroo, Vijay K. Broad Institute of MIT and Harvard Regev, Aviv Th17 cells are key players in defense against pathogens and maintaining tissue homeostasis, but also act as critical drivers of autoimmune diseases. Based on single-cell RNA-seq profiling of pathogenic versus nonpathogenic Th17 cells, we identified protein C receptor (PROCR) as a cell surface molecule expressed in covariance with the regulatory module of Th17 cells. Although PROCR expression in T cells was controlled by the cooperative action of the Th17 lineage-specific transcription factors RORγt, IRF4, and STAT3, PROCR negatively regulated Th17 differentiation. CD4+ T cells from PROCR low expressor mutant mice readily differentiated into Th17 cells, whereas addition of the PROCR ligand, activated protein C, inhibited Th17 differentiation in vitro. In addition, PROCR acted as a negative regulator of Th17 pathogenicity in that it down-regulated expression of several pathogenic signature genes, including IL-1 and IL-23 receptors. Furthermore, T cell–specific deficiency of PROCR resulted in the exacerbation of experimental autoimmune encephalomyelitis (EAE) and higher frequencies of Th17 cell in vivo, indicating that PROCR also inhibits pathogenicity of Th17 cells in vivo. PROCR thus does not globally inhibit Th17 responses but could be targeted to selectively inhibit proinflammatory Th17 cells. 2017-05-02T17:41:05Z 2017-05-02T17:41:05Z 2016-09 2015-07 Article http://purl.org/eprint/type/JournalArticle 0022-1007 1540-9538 http://hdl.handle.net/1721.1/108596 Kishi, Yasuhiro; Kondo, Takaaki; Xiao, Sheng; Yosef, Nir; Gaublomme, Jellert; Wu, Chuan; Wang, Chao, et al. “Protein C Receptor (PROCR) Is a Negative Regulator of Th17 Pathogenicity.” The Journal of Experimental Medicine 213, no. 11 (September 2016): 2489–2501. © 2016 Kishi et al. https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1084/jem.20151118 Journal of Experimental Medicine Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Rockefeller University Press, The Rockefeller University Press |
| spellingShingle | Kishi, Yasuhiro Kondo, Takaaki Xiao, Sheng Yosef, Nir Gaublomme, Jellert Wu, Chuan Wang, Chao Chihara, Norio Regev, Aviv Joller, Nicole Kuchroo, Vijay K. Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity |
| title | Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity |
| title_full | Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity |
| title_fullStr | Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity |
| title_full_unstemmed | Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity |
| title_short | Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity |
| title_sort | protein c receptor procr is a negative regulator of th17 pathogenicity |
| url | http://hdl.handle.net/1721.1/108596 https://orcid.org/0000-0001-8567-2049 |
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