دورية أكاديمية
Rho-kinase inhibitor alleviates CD4 + T cell mediated corneal graft rejection by modulating its STAT3 and STAT5 activation.
| العنوان: | Rho-kinase inhibitor alleviates CD4 + T cell mediated corneal graft rejection by modulating its STAT3 and STAT5 activation. |
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| المؤلفون: | Li S; Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Lab, Beijing, China., Zhang P; Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Lab, Beijing, China., Li A; Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Lab, Beijing, China., Bao J; Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Lab, Beijing, China., Pan Z; Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Lab, Beijing, China., Jie Y; Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Lab, Beijing, China. Electronic address: jie_yingcn@aliyun.com. |
| المصدر: | Experimental eye research [Exp Eye Res] 2024 May; Vol. 242, pp. 109857. Date of Electronic Publication: 2024 Mar 11. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: England NLM ID: 0370707 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0007 (Electronic) Linking ISSN: 00144835 NLM ISO Abbreviation: Exp Eye Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: London : Academic Press Original Publication: London. |
| مواضيع طبية MeSH: | Graft Rejection*/metabolism , Graft Rejection*/prevention & control , rho-Associated Kinases*/antagonists & inhibitors , CD4-Positive T-Lymphocytes*/immunology , STAT3 Transcription Factor*/metabolism , Mice, Inbred C57BL* , Mice, Inbred BALB C* , STAT5 Transcription Factor*/metabolism , Amides*/pharmacology , Amides*/therapeutic use , Pyridines*/pharmacology , Pyridines*/therapeutic use, Animals ; Mice ; Disease Models, Animal ; Phosphorylation ; Flow Cytometry ; Keratoplasty, Penetrating ; Blotting, Western ; Corneal Transplantation ; Male |
| مستخلص: | Penetrating keratoplasty remains the most common treatment to restore vision for corneal diseases. Immune rejection after corneal transplantation is one of the major causes of graft failure. In recent years, Rho-associated protein kinase (ROCK) inhibitors have been found to be associated with the activation of the STATs pathway and are widely studied in autoimmune diseases. Therefore, it may be possible that the ROCK inhibitors also participate in the local and systemic immune regulation in corneal transplantation through activation of the STATs pathway and affect the CD4 + T cell differentiation. This study aimed to explore the role of ROCK-STATs pathway in the occurrence of immune rejection in corneal transplantation by applying Y27632, a ROCK inhibitor, to the recipient mice and peripheral CD4 + T cells. We found that Y27632 significantly up-regulated the phosphorylation level of STAT5 in both spleen and lymph nodes, down-regulated the phosphorylation level of STAT3 in the CD4 + T cells in the spleen. It also increased the proportion of CD4 + CD25 + Foxp3 + Helios + Tregs while decreased CD4 + IL17A + -Th17 cells. Moreover, Y27632 also reduced the proportion of dendritic cells in both spleen and lymph nodes, as well as the expression level of CD86 on their surfaces in the spleen, while the proportion of macrophages was not affected. The expression levels of ROCK1, ROCK2, CD11c and IL-17A mRNA were also found to be low in the graft tissue while the expression of Helios was upregulated. Rho-kinase inhibitor can modulate the balance of Tregs/Th17 by regulating the phosphorylation levels of both STAT3 and STAT5, thereby inhibiting the occurrence of immune rejection in allogeneic corneal transplantation. (Copyright © 2024 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Corneal transplantation; STAT; Th17; Treg; Y27632 |
| المشرفين على المادة: | EC 2.7.11.1 (rho-Associated Kinases) 0 (STAT3 Transcription Factor) 0 (STAT5 Transcription Factor) 0 (Amides) 0 (Pyridines) 138381-45-0 (Y 27632) 0 (Stat3 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20240313 Date Completed: 20240426 Latest Revision: 20240426 |
| رمز التحديث: | 20240427 |
| DOI: | 10.1016/j.exer.2024.109857 |
| PMID: | 38479724 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-0007 |
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| DOI: | 10.1016/j.exer.2024.109857 |