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Anti-TL1A monoclonal antibody modulates the dysregulation of Th1/Th17 cells and attenuates granuloma formation in sarcoidosis by inhibiting the PI3K/AKT signaling pathway.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2024 Aug 20; Vol. 137, pp. 112360. Date of Electronic Publication: 2024 Jun 08. - Publication Year :
- 2024
-
Abstract
- 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.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- 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
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
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 137
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38852524
- Full Text :
- https://doi.org/10.1016/j.intimp.2024.112360