دورية أكاديمية
Iguratimod ameliorates antibody-mediated rejection after renal transplant by modulating the Th17/Treg paradigm.
| العنوان: | Iguratimod ameliorates antibody-mediated rejection after renal transplant by modulating the Th17/Treg paradigm. |
|---|---|
| المؤلفون: | Lu H; Department of Urology, Wuxi People's Hospital Affiliated to Nanjing Medical University, 299 Qingyang Road, Wuxi 214023, Jiangsu, People's Republic of China., Sun X; Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, 121# Jiangjiayuan Road, Nanjing, Jiangsu, People's Republic of China., Yang C; Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, 121# Jiangjiayuan Road, Nanjing, Jiangsu, People's Republic of China., Zheng M; Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, 121# Jiangjiayuan Road, Nanjing, Jiangsu, People's Republic of China., Ni B; Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, 121# Jiangjiayuan Road, Nanjing, Jiangsu, People's Republic of China., Han Z; Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, Jiangsu, People's Republic of China., Tao J; Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, Jiangsu, People's Republic of China., Ju X; Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, Jiangsu, People's Republic of China., Tan R; Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, Jiangsu, People's Republic of China., Shen B; Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, 121# Jiangjiayuan Road, Nanjing, Jiangsu, People's Republic of China. Electronic address: baixinshen@njmu.eud.cn., Gu M; Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, 121# Jiangjiayuan Road, Nanjing, Jiangsu, People's Republic of China; Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, Jiangsu, People's Republic of China. Electronic address: lancetgu@aliyun.com., Wang Z; Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing, Jiangsu, People's Republic of China. Electronic address: wangzijie@njmu.edu.cn. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2024 Jul 30; Vol. 136, pp. 112409. Date of Electronic Publication: 2024 Jun 07. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Th17 Cells*/immunology , T-Lymphocytes, Regulatory*/immunology , Kidney Transplantation* , Graft Rejection*/immunology , Mice, Inbred BALB C* , Mice, Inbred C57BL* , Chromones*/pharmacology, Animals ; Mice ; Male ; Immunosuppressive Agents/therapeutic use ; Humans ; Cell Differentiation/drug effects ; Disease Models, Animal ; Cells, Cultured ; Sulfonamides |
| مستخلص: | Background: Iguratimod (IGU) is widely used in clinical practice due to its stable anti-inflammatory effects. Our previous studies have confirmed that the proportion of Th17/Treg balance in patients taking IGU altered significantly. This study aims to explore the role of IGU in antibody-mediated rejection (ABMR) and its potential mechanisms. Methods: We conducted bioinformatics analysis of sequencing data from the GEO database to analyze the abundance of immune cell infiltration in transplanted kidney tissues. In vivo, IGU was intervened in a mice secondary skin transplantation model and a mice kidney transplantation ABMR model, and histological morphology of the grafts were examined by pathological staining, while relevant indicators were determined through qRT-PCR, immunohistochemistry, and enzyme-linked immunosorbent assay, observed T cell differentiation by flow cytometry, and preliminarily assessed the immunosuppressive effect of IGU. In vitro, we established Th17 and Treg cell induction and stimulation differentiation culture systems and added IGU for intervention to explore its effects on their differentiation. Results: Through bioinformatics analysis, we found that Th17 and Treg may play important roles in the occurrence and development of ABMR. In vivo, we found that IGU could effectively reduce the damage caused by ABMR to the grafts, alleviate the infiltration of inflammatory cells in the graft tissues, and reduce the deposition of C4d in the grafts. Moreover, it is also found that IGU regulated the differentiation of Th17 and Treg cells in the spleen and peripheral blood and reduced the expression of IL-17A in the grafts and serum. In addition, same changes were observed in the induction and differentiation culture system of Th17 and Treg cells in vitro after the addition of IGU. Conclusion: IGU can inhibit the progression of ABMR by regulating the differentiation of Th17 and Treg cells, providing novel insights for optimizing clinical immunosuppressive treatment regimens. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: IL-17A; Iguratimod; JAK-STAT; Kidney transplantation; Th17/Treg |
| المشرفين على المادة: | 4IHY34Y2NV (iguratimod) 0 (Chromones) 0 (Immunosuppressive Agents) 0 (Sulfonamides) |
| تواريخ الأحداث: | Date Created: 20240608 Date Completed: 20240615 Latest Revision: 20240615 |
| رمز التحديث: | 20240616 |
| DOI: | 10.1016/j.intimp.2024.112409 |
| PMID: | 38850789 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
|---|---|
| DOI: | 10.1016/j.intimp.2024.112409 |