Article: Glucocorticoid-induced tumor necrosis factor receptor family-related protein exacerbates collagen-induced arthritis by enhancing the expansion of Th17 cells

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TitleGlucocorticoid-induced tumor necrosis factor receptor family-related protein exacerbates collagen-induced arthritis by enhancing the expansion of Th17 cells
AuthorsWang, S1 2
Shi, Y1
Yang, M3
Ma, J1
Tian, J1
Chen, J1
Mao, C1
Jiao, Z1
Ko, KH3
Baidoo, SE1
Xu, H1
Hua, Z2
Lu, L2 3
Issue Date2012
PublisherElsevier Inc.. The Journal's web site is located at http://ajp.amjpathol.org/
CitationThe American Journal of Pathology: cellular and molecular biology of disease, 2012, v. 180 n. 3, p. 1059-1067 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.ajpath.2011.11.018
AbstractRheumatoid arthritis (RA), a chronic autoimmune form of inflammatory joint disease, progressively affects multiple joints with pathological changes in the synovia, cartilage, and bone. Numerous studies have suggested a critical role for glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) in the pathogenesis of autoimmune arthritis by modulating both innate and adaptive immune reactions, but the underlying mechanisms by which GITR activation promotes arthritic progression remain largely unclear. In this study, we found that collagen-induced arthritis mice treated with the ligand of GITR (GITRL) displayed an earlier onset of arthritis with a markedly increased severity of arthritic symptoms and joint damage, in which significantly increased Th17 cells in both spleen and draining lymph nodes were observed. Notably, results showed that a marked expansion of Th17 cells with increased RORgammat mRNA expression was induced from naive CD4(+) T cells when cultured with GITRL. Consistently, normal mice that were treated with GITRL were found to display a substantial expansion of splenic Th17 cells. Furthermore, we detected elevated serum levels of GITRL in patients with RA, which were positively correlated with an increase in interleukin-17 production. Taken together, the results from this study have revealed a new function of GITRL in exacerbating autoimmune arthritis via the enhancement of the expansion of Th17 cells.
ISSN0002-9440
2011 Impact Factor: 4.89
2011 SCImago Journal Rankings: 0.697
DOIhttp://dx.doi.org/10.1016/j.ajpath.2011.11.018
DC Field
Value
dc.contributor.authorWang, S
dc.contributor.authorShi, Y
dc.contributor.authorYang, M
dc.contributor.authorMa, J
dc.contributor.authorTian, J
dc.contributor.authorChen, J
dc.contributor.authorMao, C
dc.contributor.authorJiao, Z
dc.contributor.authorKo, KH
dc.contributor.authorBaidoo, SE
dc.contributor.authorXu, H
dc.contributor.authorHua, Z
dc.contributor.authorLu, L
dc.date.accessioned2012-09-20T08:10:43Z
dc.date.available2012-09-20T08:10:43Z
dc.date.issued2012
dc.description.abstractRheumatoid arthritis (RA), a chronic autoimmune form of inflammatory joint disease, progressively affects multiple joints with pathological changes in the synovia, cartilage, and bone. Numerous studies have suggested a critical role for glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) in the pathogenesis of autoimmune arthritis by modulating both innate and adaptive immune reactions, but the underlying mechanisms by which GITR activation promotes arthritic progression remain largely unclear. In this study, we found that collagen-induced arthritis mice treated with the ligand of GITR (GITRL) displayed an earlier onset of arthritis with a markedly increased severity of arthritic symptoms and joint damage, in which significantly increased Th17 cells in both spleen and draining lymph nodes were observed. Notably, results showed that a marked expansion of Th17 cells with increased RORgammat mRNA expression was induced from naive CD4(+) T cells when cultured with GITRL. Consistently, normal mice that were treated with GITRL were found to display a substantial expansion of splenic Th17 cells. Furthermore, we detected elevated serum levels of GITRL in patients with RA, which were positively correlated with an increase in interleukin-17 production. Taken together, the results from this study have revealed a new function of GITRL in exacerbating autoimmune arthritis via the enhancement of the expansion of Th17 cells.
dc.identifier.citationThe American Journal of Pathology: cellular and molecular biology of disease, 2012, v. 180 n. 3, p. 1059-1067 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.ajpath.2011.11.018
dc.identifier.citeulike10625413
dc.identifier.doihttp://dx.doi.org/10.1016/j.ajpath.2011.11.018
dc.identifier.epage1067
dc.identifier.hkuros208155
dc.identifier.issn0002-9440
2011 Impact Factor: 4.89
2011 SCImago Journal Rankings: 0.697
dc.identifier.issue3
dc.identifier.openurl
dc.identifier.pmid22214837
dc.identifier.scopuseid_2-s2.0-84863171449
dc.identifier.spage1059
dc.identifier.urihttp://hdl.handle.net/10722/164840
dc.identifier.volume180
dc.languageeng
dc.publisherElsevier Inc.. The Journal's web site is located at http://ajp.amjpathol.org/
dc.publisher.placeUnited States
dc.relation.ispartofThe American Journal of Pathology: cellular and molecular biology of disease
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in . Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in PUBLICATION, [VOL#, ISSUE#, (DATE)] DOI#
dc.subject.meshArthritis, Experimental - etiology - pathology
dc.subject.meshCD4-Positive T-Lymphocytes - metabolism
dc.subject.meshCell Differentiation
dc.subject.meshGlucocorticoid-Induced TNFR-Related Protein - metabolism - pharmacology - physiology
dc.subject.meshTh17 Cells - metabolism - pathology
dc.titleGlucocorticoid-induced tumor necrosis factor receptor family-related protein exacerbates collagen-induced arthritis by enhancing the expansion of Th17 cells
dc.typeArticle
Author Affiliations
  1. Jiangsu University
  2. Nanjing University
  3. The University of Hong Kong