Cystatin C regulates major histocompatibility complex‐II –peptide presentation and extracellular signal‐regulated kinase‐dependent polarizing cytokine production by bone marrow‐derived dendritic cells
| العنوان: | Cystatin C regulates major histocompatibility complex‐ |
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| المؤلفون: | Shuangchao Liang, Shun Chen, Wenjie Zhang, Yuekang Xu, Mengting Zi, Yifan Zhan, Shan Liu, Jiqiong Hu, Lei Liu, Fengge Wang, Li Sun, Andrew M. Lew, Yanfang Zhao |
| المصدر: | Immunology & Cell Biology. 97:916-930 |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Proteases, medicine.medical_treatment, Immunology, Antigen presentation, Bone Marrow Cells, Nitric Oxide, Major histocompatibility complex, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Animals, Immunology and Allergy, Cystatin C, Extracellular Signal-Regulated MAP Kinases, Cell Proliferation, Antigen Presentation, biology, Chemistry, Histocompatibility Antigens Class II, Cell Polarity, Cell Differentiation, Dendritic Cells, Cell Biology, Dendritic cell, Th1 Cells, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, Cytokine, biology.protein, Cytokines, Th17 Cells, Cystatin, Peptides, Chickens, 030215 immunology |
| الوصف: | Cystatin C is a ubiquitously expressed cysteine protease inhibitor that protects cells from either improper hydrolysis by endogenous proteases or pathogen growth/virulence by exogenous proteases. Although commonly used as a serum biomarker for evaluating renal function, cystatin C is associated with many immunological disorders under various pathophysiological conditions. How cystatin C affects immune cells, especially dendritic cells (DCs), however, is far from clear. In this study, we found that pharmacological treatment with or genetic overexpression of cystatin C in bone marrow-derived DCs (BMDCs) reduced their capacity to stimulate CD4+ T-cell proliferation, despite increased antigen uptake. This reduced capacity corresponded with reduced major histocompatibility complex-II presentation owing to diminished levels of the chaperon H2-DM in BMDCs. Instead of promoting proliferation, cystatin C promoted skewing of T cells toward proinflammatory T-helper (Th)1/Th17 differentiation. This was mediated by augmented extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase phosphorylation in BMDCs, leading to secretion of polarizing cytokines, which in turn led to the Th deviation. Collectively, our study explained the cellular and molecular basis of how this protease inhibitor can regulate immune responses, namely by affecting BMDCs and their cytokine pathway. Our results might open up an avenue for the development of therapeutic agents for the treatment of cystatin C-related immunological diseases. |
| تدمد: | 1440-1711 0818-9641 |
| DOI: | 10.1111/imcb.12290 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d459d5bcf41f6d0f104539cb6fa0c277 https://doi.org/10.1111/imcb.12290 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d459d5bcf41f6d0f104539cb6fa0c277 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14401711 08189641 |
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| DOI: | 10.1111/imcb.12290 |