Academic Journal
CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis
| العنوان: | CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis |
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| المؤلفون: | Kanin Salao, Lele Jiang, Hui Li, Vicky W.-W. Tsai, Yasmin Husaini, Paul M. G. Curmi, Louise J. Brown, David A. Brown, Samuel N. Breit |
| المصدر: | Biology Open, Vol 5, Iss 5, Pp 620-630 (2016) |
| بيانات النشر: | The Company of Biologists, 2016. |
| سنة النشر: | 2016 |
| المجموعة: | LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | CLIC1, Dendritic cells, Phagosome, Acidification, Proteolysis, Antigen presentation, Science, Biology (General), QH301-705.5 |
| الوصف: | Intracellular chloride channel protein 1 (CLIC1) participates in inflammatory processes by regulating macrophage phagosomal functions such as pH and proteolysis. Here, we sought to determine if CLIC1 can regulate adaptive immunity by actions on dendritic cells (DCs), the key professional antigen presenting cells. To do this, we first generated bone marrow-derived DCs (BMDCs) from germline CLIC1 gene-deleted (CLIC1−/−) and wild-type (CLIC1+/+) mice, then studied them in vitro and in vivo. We found phagocytosis triggered cytoplasmic CLIC1 translocation to the phagosomal membrane where it regulated phagosomal pH and proteolysis. Phagosomes from CLIC1−/− BMDCs displayed impaired acidification and proteolysis, which could be reproduced if CLIC1+/+, but not CLIC1−/− cells, were treated with IAA94, a CLIC family ion channel blocker. CLIC1−/− BMDC displayed reduced in vitro antigen processing and presentation of full-length myelin oligodendrocyte glycoprotein (MOG) and reduced MOG-induced experimental autoimmune encephalomyelitis. These data suggest that CLIC1 regulates DC phagosomal pH to ensure optimal processing of antigen for presentation to antigen-specific T-cells. Further, they indicate that CLIC1 is a novel therapeutic target to help reduce the adaptive immune response in autoimmune diseases. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2046-6390 |
| Relation: | http://bio.biologists.org/content/5/5/620; https://doaj.org/toc/2046-6390 |
| DOI: | 10.1242/bio.018119 |
| URL الوصول: | https://doaj.org/article/f319230c8c664cfd895040d0dc894b41 |
| رقم الانضمام: | edsdoj.f319230c8c664cfd895040d0dc894b41 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20466390 |
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| DOI: | 10.1242/bio.018119 |