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DC Field | Value | Language |
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dc.contributor.author | Richard Kitching A. | en |
dc.contributor.author | Godfrey A.S. | en |
dc.contributor.author | Ooi J.D. | en |
dc.contributor.author | O'sullivan K.-M. | en |
dc.contributor.author | Oudin V. | en |
dc.contributor.author | Holdsworth S.R. | en |
dc.contributor.author | Gan P.-Y. | en |
dc.date.accessioned | 2021-05-14T12:12:02Z | en |
dc.date.available | 2021-05-14T12:12:02Z | en |
dc.date.copyright | 2019 | en |
dc.date.created | 20190917 | en |
dc.date.issued | 2019-09-17 | en |
dc.identifier.citation | Journal of the American Society of Nephrology. 30 (8) (pp 1365-1374), 2019. Date of Publication: August 2019. | en |
dc.identifier.issn | 1046-6673 | en |
dc.identifier.uri | https://repository.monashhealth.org/monashhealthjspui/handle/1/36014 | en |
dc.description.abstract | Background Myeloperoxidase (MPO)-ANCA-associated GN is a significant cause of renal failure. Manipulating autoimmunity by inducing regulatory T cells is potentially a more specific and safer therapeutic option than conventional immunosuppression. Methods To generate MPO-specific regulatory T cells, we used a modified protein-conjugating compound, 1-ethyl-3-(3'dimethylaminopropyl)-carbodiimide (ECDI), to couple the immunodominant MPO peptide (MPO409-428) or a control ovalbumin peptide (OVA323-339) to splenocytes and induced apoptosis in the conjugated cells. We then administered MPO-and OVA-conjugated apoptotic splenocytes (MPO-Sps and OVA-Sps, respectively) to mice and compared their effects on development and severity of anti-MPO GN. We induced autoimmunity to MPO by immunizing mice with MPO in adjuvant; to trigger GN, we used low-dose antiglomerular basement membrane globulin, which transiently recruits neutro-phils that deposit MPO in glomeruli. We also compared the effects of transferring CD4+ T cells from mice treated with MPO-Sp or OVA-Sp to recipient mice with established anti-MPO autoimmunity. Results MPO-Sp but not OVA-Sp administration increased MPO-specific, peripherally derived CD4+ Foxp3- type 1 regulatory T cells and reduced anti-MPO autoimmunity and GN. However, in mice depleted of regulatory T cells, MPO-Sp administration did not protect from anti-MPO autoimmunity or GN. Mice with established anti-MPO autoimmunity that received CD4+ T cells transferred from mice treated with MPO-Sp (but not CD4+ T cells transferred from mice treated with OVA-Sp) were protected from anti-MPO autoimmunity and GN, confirming the induction of therapeutic antigen-specific regulatory T cells. Conclusions These findings in a mouse model indicate that administering apoptotic splenocytes conjugated with the immunodominant MPO peptide suppresses anti-MPO GN by inducing antigen-specific tolerance.Copyright © 2019 by the American Society of Nephrology. | en |
dc.language | English | en |
dc.language | en | en |
dc.publisher | American Society of Nephrology (E-mail: email@asn-online.org) | en |
dc.relation.ispartof | Journal of the American Society of Nephrology | en |
dc.title | Apoptotic cell-induced, antigen-specific immunoregulation to treat experimental antimyeloperoxidase GN. | en |
dc.type | Article | en |
dc.identifier.doi | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1681/ASN.2018090955 | en |
dc.publisher.place | United States | en |
dc.identifier.pubmedid | 31337690 [http://www.ncbi.nlm.nih.gov/pubmed/?term=31337690] | en |
dc.identifier.source | 2002545998 | en |
dc.identifier.institution | (Gan, Godfrey, Ooi, O'sullivan, Oudin, Richard Kitching, Holdsworth) Department of Medicine, Centre for Inflammatory Diseases, Monash University, Clayton, VIC, Australia (Gan, Holdsworth) Department of Immunology, Monash Health, Clayton, VIC, Australia (Richard Kitching, Holdsworth) Department of Nephrology, Monash Health, Clayton, VIC, Australia (Richard Kitching) Department of Pediatric Nephrology, Monash Health, Clayton, VIC, Australia | en |
dc.description.address | P.-Y. Gan, Centre for Inflammatory Diseases, Monash University, Department of Medicine, Monash Medical Centre, Clayton, VIC 3168, Australia. E-mail: Poh-yi.gan@monash.edu | en |
dc.description.publicationstatus | Embase | en |
dc.rights.statement | Copyright 2019 Elsevier B.V., All rights reserved. | en |
dc.identifier.authoremail | Gan P.-Y.; Poh-yi.gan@monash.edu | en |
dc.description.grant | No: 1147388 Organization: (NHMRC) *National Health and Medical Research Council* Organization No: 501100000925 Country: Australia | en |
item.fulltext | No Fulltext | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.openairetype | Article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
crisitem.author.dept | Immunology and Allergy | - |
Appears in Collections: | Articles |
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