CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis
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 pre...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
The Company of Biologists
2016-05-01
|
Series: | Biology Open |
Subjects: | |
Online Access: | http://bio.biologists.org/content/5/5/620 |
id |
doaj-f319230c8c664cfd895040d0dc894b41 |
---|---|
record_format |
Article |
spelling |
doaj-f319230c8c664cfd895040d0dc894b412021-06-02T19:00:21ZengThe Company of BiologistsBiology Open2046-63902016-05-015562063010.1242/bio.018119018119CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysisKanin Salao0Lele Jiang1Hui Li2Vicky W.-W. Tsai3Yasmin Husaini4Paul M. G. Curmi5Louise J. Brown6David A. Brown7Samuel N. Breit8 St Vincent's Centre for Applied Medical Research, St. Vincent's Hospital and University of New South Wales, Sydney, New South Wales 2010, Australia St Vincent's Centre for Applied Medical Research, St. Vincent's Hospital and University of New South Wales, Sydney, New South Wales 2010, Australia St Vincent's Centre for Applied Medical Research, St. Vincent's Hospital and University of New South Wales, Sydney, New South Wales 2010, Australia St Vincent's Centre for Applied Medical Research, St. Vincent's Hospital and University of New South Wales, Sydney, New South Wales 2010, Australia St Vincent's Centre for Applied Medical Research, St. Vincent's Hospital and University of New South Wales, Sydney, New South Wales 2010, Australia School of Physics, University of New South Wales, Sydney, New South Wales 2052, Australia Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, New South Wales 2109, Australia St Vincent's Centre for Applied Medical Research, St. Vincent's Hospital and University of New South Wales, Sydney, New South Wales 2010, Australia St Vincent's Centre for Applied Medical Research, St. Vincent's Hospital and University of New South Wales, Sydney, New South Wales 2010, Australia 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.http://bio.biologists.org/content/5/5/620CLIC1Dendritic cellsPhagosomeAcidificationProteolysisAntigen presentation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis Biology Open CLIC1 Dendritic cells Phagosome Acidification Proteolysis Antigen presentation |
author_facet |
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 |
author_sort |
Kanin Salao |
title |
CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis |
title_short |
CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis |
title_full |
CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis |
title_fullStr |
CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis |
title_full_unstemmed |
CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis |
title_sort |
clic1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis |
publisher |
The Company of Biologists |
series |
Biology Open |
issn |
2046-6390 |
publishDate |
2016-05-01 |
description |
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. |
topic |
CLIC1 Dendritic cells Phagosome Acidification Proteolysis Antigen presentation |
url |
http://bio.biologists.org/content/5/5/620 |
work_keys_str_mv |
AT kaninsalao clic1regulatesdendriticcellantigenprocessingandpresentationbymodulatingphagosomeacidificationandproteolysis AT lelejiang clic1regulatesdendriticcellantigenprocessingandpresentationbymodulatingphagosomeacidificationandproteolysis AT huili clic1regulatesdendriticcellantigenprocessingandpresentationbymodulatingphagosomeacidificationandproteolysis AT vickywwtsai clic1regulatesdendriticcellantigenprocessingandpresentationbymodulatingphagosomeacidificationandproteolysis AT yasminhusaini clic1regulatesdendriticcellantigenprocessingandpresentationbymodulatingphagosomeacidificationandproteolysis AT paulmgcurmi clic1regulatesdendriticcellantigenprocessingandpresentationbymodulatingphagosomeacidificationandproteolysis AT louisejbrown clic1regulatesdendriticcellantigenprocessingandpresentationbymodulatingphagosomeacidificationandproteolysis AT davidabrown clic1regulatesdendriticcellantigenprocessingandpresentationbymodulatingphagosomeacidificationandproteolysis AT samuelnbreit clic1regulatesdendriticcellantigenprocessingandpresentationbymodulatingphagosomeacidificationandproteolysis |
_version_ |
1721402011855880192 |