IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Primary Sjögren’s Syndrome Patients
ObjectiveTo investigate the role of IL-2 in the balance of Th17 and Tregs and elucidate the underlying mechanisms of enhanced Th17 differentiation in primary Sjögren’s syndrome (pSS) patients.MethodsThis study involved 31 pSS patients, 7 Sicca patients, and 31 healthy subjects. Th17 and Treg cells w...
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01755/full |
| _version_ | 1819206327096836096 |
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| author | Jing Luo Bingxia Ming Cai Zhang Xiaofei Deng Pingfei Li Zhengping Wei Yu Xia Kan Jiang Hong Ye Wanli Ma Zheng Liu Huabin Li Xiang-Ping Yang Lingli Dong |
| author_facet | Jing Luo Bingxia Ming Cai Zhang Xiaofei Deng Pingfei Li Zhengping Wei Yu Xia Kan Jiang Hong Ye Wanli Ma Zheng Liu Huabin Li Xiang-Ping Yang Lingli Dong |
| author_sort | Jing Luo |
| collection | DOAJ |
| description | ObjectiveTo investigate the role of IL-2 in the balance of Th17 and Tregs and elucidate the underlying mechanisms of enhanced Th17 differentiation in primary Sjögren’s syndrome (pSS) patients.MethodsThis study involved 31 pSS patients, 7 Sicca patients, and 31 healthy subjects. Th17 and Treg cells were determined by flow cytometry, and IL-17A was detected by immunohistochemistry. IL-2 and IL-6 levels were assessed by ELISA and qPCR. p-STAT5 and p-STAT3 in salivary glands (SGs) were evaluated by immunohistochemistry and flow cytometry. The binding of STAT5 and STAT3 to the Il17a gene locus was measured by chromatin immunoprecipitation.ResultsWe found that the percentage of Th17 cells was increased in the periphery and SG of pSS patients when compared with healthy subjects, but the Treg cells was unchanged. Meanwhile, the IL-2 level was reduced, and the IL-6 and IL-17A level was increased in the plasma of pSS patients. The ratio of IL-2 and IL-6 level was also decreased and IL-2 level was negatively correlated with the level of IL-17A. The expression of Il6 and Il17a mRNA was significantly increased, whereas Foxp3, Tgfb1, Tnfa, and Ifng mRNA were comparable. Furthermore, the level of STAT5 phosphorylation (p-STAT5) was reduced and p-STAT3 was enhanced in the SGs and in peripheral CD4+ T cells of pSS patients. In vitro IL-2 treatment-induced STAT5 competed with STAT3 binding in human Il17a locus, leading to decreased Th17 differentiation, which was associated with the reduced transcription activation marker H3K4me3.ConclusionOur findings demonstrated a Treg-independent upregulation of Th17 generation in pSS, which is likely due to a lack of IL-2-mediated suppression of Th17 differentiation. This study identified a novel mechanism of IL-2-mediated immune suppression in pSS. |
| first_indexed | 2024-12-23T05:05:50Z |
| format | Article |
| id | doaj.art-cc1d4ab7039a42ef9fd1a4a7de85f343 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T05:05:50Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-cc1d4ab7039a42ef9fd1a4a7de85f3432022-12-21T17:59:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-08-01910.3389/fimmu.2018.01755398405IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Primary Sjögren’s Syndrome PatientsJing Luo0Bingxia Ming1Cai Zhang2Xiaofei Deng3Pingfei Li4Zhengping Wei5Yu Xia6Kan Jiang7Hong Ye8Wanli Ma9Zheng Liu10Huabin Li11Xiang-Ping Yang12Lingli Dong13Department of Immunology, School of Basic Medicine, Tongji Medical School, Huazhong University of Science and Technology (HUST), Wuhan, ChinaDepartment of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology (HUST), Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical School, Huazhong University of Science and Technology (HUST), Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical School, Huazhong University of Science and Technology (HUST), Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical School, Huazhong University of Science and Technology (HUST), Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical School, Huazhong University of Science and Technology (HUST), Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical School, Huazhong University of Science and Technology (HUST), Wuhan, ChinaLymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United StatesDepartment of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, ChinaDepartment of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology (HUST), Wuhan, ChinaDepartment of Otolaryngology, Head and Neck Surgery, Affiliated Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical School, Huazhong University of Science and Technology (HUST), Wuhan, ChinaDepartment of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology (HUST), Wuhan, ChinaObjectiveTo investigate the role of IL-2 in the balance of Th17 and Tregs and elucidate the underlying mechanisms of enhanced Th17 differentiation in primary Sjögren’s syndrome (pSS) patients.MethodsThis study involved 31 pSS patients, 7 Sicca patients, and 31 healthy subjects. Th17 and Treg cells were determined by flow cytometry, and IL-17A was detected by immunohistochemistry. IL-2 and IL-6 levels were assessed by ELISA and qPCR. p-STAT5 and p-STAT3 in salivary glands (SGs) were evaluated by immunohistochemistry and flow cytometry. The binding of STAT5 and STAT3 to the Il17a gene locus was measured by chromatin immunoprecipitation.ResultsWe found that the percentage of Th17 cells was increased in the periphery and SG of pSS patients when compared with healthy subjects, but the Treg cells was unchanged. Meanwhile, the IL-2 level was reduced, and the IL-6 and IL-17A level was increased in the plasma of pSS patients. The ratio of IL-2 and IL-6 level was also decreased and IL-2 level was negatively correlated with the level of IL-17A. The expression of Il6 and Il17a mRNA was significantly increased, whereas Foxp3, Tgfb1, Tnfa, and Ifng mRNA were comparable. Furthermore, the level of STAT5 phosphorylation (p-STAT5) was reduced and p-STAT3 was enhanced in the SGs and in peripheral CD4+ T cells of pSS patients. In vitro IL-2 treatment-induced STAT5 competed with STAT3 binding in human Il17a locus, leading to decreased Th17 differentiation, which was associated with the reduced transcription activation marker H3K4me3.ConclusionOur findings demonstrated a Treg-independent upregulation of Th17 generation in pSS, which is likely due to a lack of IL-2-mediated suppression of Th17 differentiation. This study identified a novel mechanism of IL-2-mediated immune suppression in pSS.https://www.frontiersin.org/article/10.3389/fimmu.2018.01755/fullSjögren syndromeIL-2TregTh17p-STAT5 |
| spellingShingle | Jing Luo Bingxia Ming Cai Zhang Xiaofei Deng Pingfei Li Zhengping Wei Yu Xia Kan Jiang Hong Ye Wanli Ma Zheng Liu Huabin Li Xiang-Ping Yang Lingli Dong IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Primary Sjögren’s Syndrome Patients Frontiers in Immunology Sjögren syndrome IL-2 Treg Th17 p-STAT5 |
| title | IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Primary Sjögren’s Syndrome Patients |
| title_full | IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Primary Sjögren’s Syndrome Patients |
| title_fullStr | IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Primary Sjögren’s Syndrome Patients |
| title_full_unstemmed | IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Primary Sjögren’s Syndrome Patients |
| title_short | IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Primary Sjögren’s Syndrome Patients |
| title_sort | il 2 inhibition of th17 generation rather than induction of treg cells is impaired in primary sjogren s syndrome patients |
| topic | Sjögren syndrome IL-2 Treg Th17 p-STAT5 |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01755/full |
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