دورية أكاديمية
HLA-B*27 Heavy Chain Homo-Oligomers Promote the Cytotoxicity of NK Cells via Activation of PI3K/AKT Signaling
| العنوان: | HLA-B*27 Heavy Chain Homo-Oligomers Promote the Cytotoxicity of NK Cells via Activation of PI3K/AKT Signaling |
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| المؤلفون: | Hui-Chun Yu, Kuang-Yung Huang, Ming-Chi Lu, Hsien-Yu Huang Tseng, Su-Qin Liu, Ning-Sheng Lai, Hsien-Bin Huang |
| المصدر: | Medicina, Vol 58, Iss 10, p 1411 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine (General) |
| مصطلحات موضوعية: | ankylosing spondylitis, human leukocytic antigen-B*27, NK cells, KIR3DL2, PI3K/AKT signaling, Medicine (General), R5-920 |
| الوصف: | Background and Objectives: Ankylosing spondylitis (AS) is a chronic inflammatory disease and is highly linked with the expression of the human leukocytic antigen-B*27 (HLA-B*27) genotype. HLA-B*27 heavy chain (B*27-HC) has an innate characteristic to slowly fold, resulting in the accumulation of the misfolded B*27-HC and the formation of homo-oligomeric B*27-HC molecules. The homo-oligomeric B*27-HC can act as a ligand of KIR3DL2. Interaction of the homo-oligomeric B*27-HC molecules with KIR3DL2 will trigger the survival and activation of KIR3DL2-positive NK cells. However, the effects of homo-oligomeric B*27-HC molecules associated with KIR3DL2 on the cytotoxic activity of NK cells and their cytokine expressions remain unknown. Materials and Methods: HLA-B*-2704-HC was overexpressed in the HMy2.C1R (C1R) cell line. Western blotting and quantitative RT-PCR were used to analyze the protein expression and cytokine expression, respectively, when C1R-B*-2704 cells that overexpress B*2704-HC were co-cultured with NK-92MI cells. Flow cytometry was used to analyze the cytotoxicity mediated by NK-92MI cells. Results: Our results revealed that NK-92MI cells up-regulated the expression of perforin and enhanced the cytotoxic activity via augmentation of PI3K/AKT signaling after co-culturing with C1R-B*2704 cells. Suppression of the dimerized B*27-HC formation or treatment with an inhibitor of PI3K, LY294002, or with an anti-B*27-HC monoclonal antibody can reduce the perforin expression of NK-92MI after co-culturing with C1R-B*-2704. Co-culturing with C1R-B*-2704 cells suppressed the TNF-α and IL6 expressions of NK-92MI cells. Conclusion: Stimulation of NK cell-mediated cytotoxicity by homo-oligomeric B*27-HC molecules may contribute to the pathogenesis of AS. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 58101411 1648-9144 1010-660X |
| Relation: | https://www.mdpi.com/1648-9144/58/10/1411; https://doaj.org/toc/1010-660X; https://doaj.org/toc/1648-9144 |
| DOI: | 10.3390/medicina58101411 |
| URL الوصول: | https://doaj.org/article/2c1efbba097c442e9370a65fad2a950c |
| رقم الأكسشن: | edsdoj.2c1efbba097c442e9370a65fad2a950c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 58101411 16489144 1010660X |
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| DOI: | 10.3390/medicina58101411 |