Regulatory TCRαβ+ Double Negative T Cells Suppress γδ T Cells and Alleviate ColitisSummary
Background and Aims: Inflammatory bowel disease arises from dysregulated immune activations triggered by a myriad of factors. The maintenance of immune tolerance within the intestinal milieu and the suppression of inflammatory responses remain the most efficacious strategies for alleviating enteriti...
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Elsevier
2025-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X25000943 |
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| author | Mingyang Li Lehan Pan Yuxi Zhang Shiyang Huang Yue Tian Dan Tian Dong Zhang |
| author_facet | Mingyang Li Lehan Pan Yuxi Zhang Shiyang Huang Yue Tian Dan Tian Dong Zhang |
| author_sort | Mingyang Li |
| collection | DOAJ |
| description | Background and Aims: Inflammatory bowel disease arises from dysregulated immune activations triggered by a myriad of factors. The maintenance of immune tolerance within the intestinal milieu and the suppression of inflammatory responses remain the most efficacious strategies for alleviating enteritis. Regulatory TCRαβ+ double-negative T (DNT) cells play pivotal roles in orchestrating the homeostasis of various organs; however, their specific influence on colitis has yet to be thoroughly elucidated. Methods: Single-cell RNA sequencing and adoptive transfer were used to delineate the distinct signatures of DNT cells and to investigate their role in the context of colitis, respectively. Results: Our observations revealed that the proportions of DNT cells within the CD3+TCRβ+NK1.1- populations in the naive murine colonic lamina propria and intraepithelial layer were significantly elevated compared with those in the mesenteric lymph node, with further augmentation noted in the colon of colitis mice. The adoptive transfer of DNT cells conferred relief from colitis symptoms. E-cadherin facilitated the interaction between DNT cells and CD103+ γδ T cells, thereby collaboratively enhancing the cytotoxicity of DNT cells against γδ T-cell populations in concert with NKG2D, ultimately promoting the remission of colitis. Furthermore, mice that received allogeneic DNT cells exhibited ameliorated colitis without inducing graft-versus-host disease. Conclusions: Among the diverse populations of DNT subsets, regulatory DNT cells are capable of accumulating in the inflamed colon, thereby preventing the progression of colitis through the suppression of CD103+ γδ T-cell responses. The adoptive transfer of DNT cells could be a novel therapeutic strategy for inflammatory bowel disease. |
| format | Article |
| id | doaj-art-add59ba22c2f40b8afd4bb83d8212040 |
| institution | OA Journals |
| issn | 2352-345X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj-art-add59ba22c2f40b8afd4bb83d82120402025-08-20T02:38:51ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2025-01-01191010155310.1016/j.jcmgh.2025.101553Regulatory TCRαβ+ Double Negative T Cells Suppress γδ T Cells and Alleviate ColitisSummaryMingyang Li0Lehan Pan1Yuxi Zhang2Shiyang Huang3Yue Tian4Dan Tian5Dong Zhang6Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing Clinical Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Disease, Beijing, China; General Surgery Department, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaNational Clinical Research Center for Digestive Disease, Beijing, China; General Surgery Department, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaNational Clinical Research Center for Digestive Disease, Beijing, China; General Surgery Department, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing Clinical Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Disease, Beijing, China; General Surgery Department, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaNational Clinical Research Center for Digestive Disease, Beijing, China; General Surgery Department, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Dan Tian, MD, 95 Yong'an Road, Beijing 100050, China.Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China; Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China; Beijing Laboratory of Oral Health, Capital Medical University School of Basic Medicine, Beijing, China; Correspondence Address correspondence to: Dong Zhang, MD, 95 Yong'an Road, Beijing 100050, China.Background and Aims: Inflammatory bowel disease arises from dysregulated immune activations triggered by a myriad of factors. The maintenance of immune tolerance within the intestinal milieu and the suppression of inflammatory responses remain the most efficacious strategies for alleviating enteritis. Regulatory TCRαβ+ double-negative T (DNT) cells play pivotal roles in orchestrating the homeostasis of various organs; however, their specific influence on colitis has yet to be thoroughly elucidated. Methods: Single-cell RNA sequencing and adoptive transfer were used to delineate the distinct signatures of DNT cells and to investigate their role in the context of colitis, respectively. Results: Our observations revealed that the proportions of DNT cells within the CD3+TCRβ+NK1.1- populations in the naive murine colonic lamina propria and intraepithelial layer were significantly elevated compared with those in the mesenteric lymph node, with further augmentation noted in the colon of colitis mice. The adoptive transfer of DNT cells conferred relief from colitis symptoms. E-cadherin facilitated the interaction between DNT cells and CD103+ γδ T cells, thereby collaboratively enhancing the cytotoxicity of DNT cells against γδ T-cell populations in concert with NKG2D, ultimately promoting the remission of colitis. Furthermore, mice that received allogeneic DNT cells exhibited ameliorated colitis without inducing graft-versus-host disease. Conclusions: Among the diverse populations of DNT subsets, regulatory DNT cells are capable of accumulating in the inflamed colon, thereby preventing the progression of colitis through the suppression of CD103+ γδ T-cell responses. The adoptive transfer of DNT cells could be a novel therapeutic strategy for inflammatory bowel disease.http://www.sciencedirect.com/science/article/pii/S2352345X25000943Regulatory DNT CellsColitisγδ T CellsE-cadherinCD103 |
| spellingShingle | Mingyang Li Lehan Pan Yuxi Zhang Shiyang Huang Yue Tian Dan Tian Dong Zhang Regulatory TCRαβ+ Double Negative T Cells Suppress γδ T Cells and Alleviate ColitisSummary Cellular and Molecular Gastroenterology and Hepatology Regulatory DNT Cells Colitis γδ T Cells E-cadherin CD103 |
| title | Regulatory TCRαβ+ Double Negative T Cells Suppress γδ T Cells and Alleviate ColitisSummary |
| title_full | Regulatory TCRαβ+ Double Negative T Cells Suppress γδ T Cells and Alleviate ColitisSummary |
| title_fullStr | Regulatory TCRαβ+ Double Negative T Cells Suppress γδ T Cells and Alleviate ColitisSummary |
| title_full_unstemmed | Regulatory TCRαβ+ Double Negative T Cells Suppress γδ T Cells and Alleviate ColitisSummary |
| title_short | Regulatory TCRαβ+ Double Negative T Cells Suppress γδ T Cells and Alleviate ColitisSummary |
| title_sort | regulatory tcrαβ double negative t cells suppress γδ t cells and alleviate colitissummary |
| topic | Regulatory DNT Cells Colitis γδ T Cells E-cadherin CD103 |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X25000943 |
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