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Article: The role of PD-1/PD-Ls in the pathogenesis of IgG4-related disease

TitleThe role of PD-1/PD-Ls in the pathogenesis of IgG4-related disease
Authors
KeywordsIgG4-RD
naïve T cell
PD-1
PD-L1
PD-L2
Treg cell
Issue Date30-Apr-2021
PublisherOxford University Press
Citation
Rheumatology, 2021, v. 61, n. 2, p. 815-825 How to Cite?
Abstract

Objective To investigate the role of programmed cell death protein 1 (PD-1) and its two ligands, PD-L1 and PD-L2, in the pathogenesis of IgG4-related disease (IgG4-RD). Methods Patients with IgG4-RD (n = 43) and healthy controls (n = 34) were recruited. Expression levels of PD-1, PD-L1 and PD-L2 in plasma, submandibular gland and T cell subsets were determined by ELISA, immunohistochemistry and flow cytometry. Naive T cells were stimulated with or without PD-L1/PD-L2 or anti-PD-L1/anti-PD-L2 for 7 days and the proportion of CD4(+)CD25(+) Treg cells was detected by flow cytometry. Results The expression of PD-1, PD-L1 and PD-L2 in the plasma, submandibular gland and on the surface of Treg cells was increased in IgG4-RD patients. Plasma soluble (s)PD-1 was positively correlated with serum IgG, IgG1, IgG3, IgG4, IgG4-RD responder index and numbers of organs involved, and negatively correlated with serum IgM, IgA, C3 and C4. Plasma sPD-L2 was positively correlated with serum IgG1, and plasma sPD-L1 was positively correlated with sPD-L2 and negatively correlated with C3. Stimulation of PD-L1 but not PD-L2 promoted the differentiation of naive T cells from IgG4-RD patients into CD4(+)CD25(+) Treg cells. Conclusion Plasma concentrations of sPD-1, sPD-L1 and sPD-L2 were significantly increased in patients with IgG4-RD, and the expression of PD-1 and PD-L2 on Treg cells was upregulated. PD-1-PD-L1 can promote the differentiation of naive T cells into Treg cells and thus participate in the pathogenesis of IgG4-RD.


Persistent Identifierhttp://hdl.handle.net/10722/333971
ISSN
2023 Impact Factor: 4.7
2023 SCImago Journal Rankings: 1.721
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, Xia-
dc.contributor.authorLu, Hui-
dc.contributor.authorPeng, Linyi-
dc.contributor.authorZhou, Jiaxin-
dc.contributor.authorWang, Mu-
dc.contributor.authorLi, Jieqiong-
dc.contributor.authorLiu, Zheng-
dc.contributor.authorZhang, Wen-
dc.contributor.authorZhao, Yan-
dc.contributor.authorZeng, Xiaofeng-
dc.contributor.authorLu, Liwei-
dc.date.accessioned2023-10-10T03:15:03Z-
dc.date.available2023-10-10T03:15:03Z-
dc.date.issued2021-04-30-
dc.identifier.citationRheumatology, 2021, v. 61, n. 2, p. 815-825-
dc.identifier.issn1462-0324-
dc.identifier.urihttp://hdl.handle.net/10722/333971-
dc.description.abstract<p></p><p>Objective To investigate the role of programmed cell death protein 1 (PD-1) and its two ligands, PD-L1 and PD-L2, in the pathogenesis of IgG4-related disease (IgG4-RD). Methods Patients with IgG4-RD (n = 43) and healthy controls (n = 34) were recruited. Expression levels of PD-1, PD-L1 and PD-L2 in plasma, submandibular gland and T cell subsets were determined by ELISA, immunohistochemistry and flow cytometry. Naive T cells were stimulated with or without PD-L1/PD-L2 or anti-PD-L1/anti-PD-L2 for 7 days and the proportion of CD4(+)CD25(+) Treg cells was detected by flow cytometry. Results The expression of PD-1, PD-L1 and PD-L2 in the plasma, submandibular gland and on the surface of Treg cells was increased in IgG4-RD patients. Plasma soluble (s)PD-1 was positively correlated with serum IgG, IgG1, IgG3, IgG4, IgG4-RD responder index and numbers of organs involved, and negatively correlated with serum IgM, IgA, C3 and C4. Plasma sPD-L2 was positively correlated with serum IgG1, and plasma sPD-L1 was positively correlated with sPD-L2 and negatively correlated with C3. Stimulation of PD-L1 but not PD-L2 promoted the differentiation of naive T cells from IgG4-RD patients into CD4(+)CD25(+) Treg cells. Conclusion Plasma concentrations of sPD-1, sPD-L1 and sPD-L2 were significantly increased in patients with IgG4-RD, and the expression of PD-1 and PD-L2 on Treg cells was upregulated. PD-1-PD-L1 can promote the differentiation of naive T cells into Treg cells and thus participate in the pathogenesis of IgG4-RD.<br></p>-
dc.languageeng-
dc.publisherOxford University Press-
dc.relation.ispartofRheumatology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectIgG4-RD-
dc.subjectnaïve T cell-
dc.subjectPD-1-
dc.subjectPD-L1-
dc.subjectPD-L2-
dc.subjectTreg cell-
dc.titleThe role of PD-1/PD-Ls in the pathogenesis of IgG4-related disease-
dc.typeArticle-
dc.identifier.doi10.1093/rheumatology/keab360-
dc.identifier.scopuseid_2-s2.0-85124434006-
dc.identifier.volume61-
dc.identifier.issue2-
dc.identifier.spage815-
dc.identifier.epage825-
dc.identifier.eissn1462-0332-
dc.identifier.isiWOS:000753121600052-
dc.identifier.issnl1462-0324-

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