The role of PD-1/PD-Ls in the pathogenesis of IgG4-related disease.
Rheumatology (Oxford)
; 61(2): 815-825, 2022 02 02.
Article
em En
| MEDLINE
| ID: mdl-33930105
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. Naïve 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 naïve 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 naïve T cells into Treg cells and thus participate in the pathogenesis of IgG4-RD.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Antígeno B7-H1
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Proteína 2 Ligante de Morte Celular Programada 1
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Receptor de Morte Celular Programada 1
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Doença Relacionada a Imunoglobulina G4
Tipo de estudo:
Etiology_studies
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Observational_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Rheumatology (Oxford)
Assunto da revista:
REUMATOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article