دورية أكاديمية
Anti-TL1A monoclonal antibody modulates the dysregulation of Th1/Th17 cells and attenuates granuloma formation in sarcoidosis by inhibiting the PI3K/AKT signaling pathway.
| العنوان: | Anti-TL1A monoclonal antibody modulates the dysregulation of Th1/Th17 cells and attenuates granuloma formation in sarcoidosis by inhibiting the PI3K/AKT signaling pathway. |
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| المؤلفون: | Ma C; Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Huang J; Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Zheng Y; Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China., Na Y; Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China., Wei J; Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Shan J; Department of Basic Medicine, Center of Translational Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, Nanjing, China., Meng K; Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China., Zhang X; Department of Basic Medicine, Center of Translational Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, Nanjing, China., Zhang S; Department of Basic Medicine, Center of Translational Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, Nanjing, China., Wen Y; Department of Basic Medicine, Center of Translational Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, Nanjing, China. Electronic address: wenyanting@nju.edu.cn., Ding J; Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China. Electronic address: dingflower@hotmail.com. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2024 Aug 20; Vol. 137, pp. 112360. Date of Electronic Publication: 2024 Jun 08. |
| 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: | Th1 Cells*/immunology , Th17 Cells*/immunology , Signal Transduction*/drug effects , Antibodies, Monoclonal*/pharmacology , Antibodies, Monoclonal*/therapeutic use , Phosphatidylinositol 3-Kinases*/metabolism , Phosphatidylinositol 3-Kinases*/immunology , Granuloma*/immunology , Granuloma*/drug therapy , Proto-Oncogene Proteins c-akt*/metabolism , Proto-Oncogene Proteins c-akt*/immunology , Tumor Necrosis Factor Ligand Superfamily Member 15*/metabolism , Tumor Necrosis Factor Ligand Superfamily Member 15*/immunology , Sarcoidosis*/immunology , Sarcoidosis*/drug therapy, Animals ; Humans ; Female ; Male ; Mice ; Adult ; Middle Aged ; Receptors, Tumor Necrosis Factor, Member 25/metabolism ; Receptors, Tumor Necrosis Factor, Member 25/immunology ; Lung/immunology ; Lung/pathology ; Cytokines/metabolism ; Cytokines/immunology ; Disease Models, Animal ; Mice, Inbred BALB C |
| مستخلص: | Sarcoidosis is a systemic granulomatous disease characterized by non-caseating epithelioid cell granulomas. One of its immunological hallmarks is the differentiation of CD4 + naïve T cells into Th1/Th17 cells, accompanied by the release of numerous pro-inflammatory cytokines. The TL1A/DR3 signaling pathway plays a crucial role in activating effector lymphocytes, thereby triggering pro-inflammatory responses. The primary aim of this investigation was to scrutinize the impact of anti-TL1A monoclonal antibody on the dysregulation of Th1/Th17 cells and granuloma formation in sarcoidosis. Initially, the abnormal activation of the TL1A/DR3 signaling pathway in pulmonary tissues of sarcoidosis patients was confirmed using qPCR and immunohistochemistry techniques. Subsequently, employing a murine model of sarcoidosis, the inhibitory effects of anti-TL1A monoclonal antibody on the TL1A/DR3 signaling pathway in sarcoidosis were investigated through qPCR, immunohistochemistry, and Western blot experiments. The influence of anti-TL1A monoclonal antibody on granulomas was assessed through HE staining, while their effects on sarcoidosis Th1/Th17 cells and associated cytokine mRNA levels were evaluated using flow cytometry and qPCR, respectively. Immunofluorescence and Western blot experiments corroborated the inhibitory effects of anti-TL1A monoclonal antibody on the aberrant activation of the PI3K/AKT signaling pathway in sarcoidosis. The findings of this study indicate that the TL1A/DR3 signaling pathway is excessively activated in sarcoidosis. Anti-TL1A monoclonal antibody effectively inhibit this abnormal activation in sarcoidosis, thereby alleviating the dysregulation of Th1/Th17 cells and reducing the formation of pulmonary granulomas. This effect may be associated with the inhibition of the downstream PI3K/AKT signaling pathway. Anti-TL1A monoclonal antibody hold promise as a potential novel therapeutic intervention for sarcoidosis. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Adaptive immunity; Anti-TL1A monoclonal antibody; Granuloma; Sarcoidosis |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) 0 (Tumor Necrosis Factor Ligand Superfamily Member 15) 0 (Receptors, Tumor Necrosis Factor, Member 25) 0 (Tnfsf15 protein, mouse) 0 (Cytokines) |
| تواريخ الأحداث: | Date Created: 20240609 Date Completed: 20240710 Latest Revision: 20240805 |
| رمز التحديث: | 20240805 |
| DOI: | 10.1016/j.intimp.2024.112360 |
| PMID: | 38852524 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2024.112360 |