CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis

Salao, K; Jiang, L; Li, H; Tsai, VWW; Husaini, Y; Curmi, PMG; Brown, LJ; Brown, DA; Breit, SN

CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis

Salao, K Jiang, L

Li, H Tsai, VWW Husaini, Y Curmi, PMG Brown, LJ Brown, DA Breit, SN

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Publication Type:: Journal Article
Citation:: Biology Open, 2016, 5 (5), pp. 620 - 630
Issue Date:: 2016-05-15

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Field	Value	Language
dc.contributor.author	Salao, K	en_US
dc.contributor.author	Jiang, L https://orcid.org/0000-0002-1326-5871	en_US
dc.contributor.author	Li, H	en_US
dc.contributor.author	Tsai, VWW	en_US
dc.contributor.author	Husaini, Y	en_US
dc.contributor.author	Curmi, PMG	en_US
dc.contributor.author	Brown, LJ	en_US
dc.contributor.author	Brown, DA	en_US
dc.contributor.author	Breit, SN	en_US
dc.date.issued	2016-05-15	en_US
dc.identifier.citation	Biology Open, 2016, 5 (5), pp. 620 - 630	en_US
dc.identifier.uri	http://hdl.handle.net/10453/117047
dc.description.abstract	© 2016, Company of Biologists Ltd. All rights reserved. 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.	en_US
dc.relation.ispartof	Biology Open	en_US
dc.relation.isbasedon	10.1242/bio.018119	en_US
dc.title	CLIC1 regulates dendritic cell antigen processing and presentation by modulating phagosome acidification and proteolysis	en_US
dc.type	Journal Article
utslib.citation.volume	5	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	0699 Other Biological Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	open_access
pubs.issue	5	en_US
pubs.publication-status	Published	en_US
pubs.volume	5	en_US

Abstract:

© 2016, Company of Biologists Ltd. All rights reserved. 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.

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http://hdl.handle.net/10453/117047