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Regulation of T Cell Activities in Rheumatoid Arthritis by the Novel Fusion Protein IgD-Fc-Ig
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and T cell hyper-activation. Emerging evidence has shown that the stimulation of immunoglobulin D (IgD) induces T cell activation and may contribute to disease pathogenesis. In this study, the sIgD concentration...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243948/ https://www.ncbi.nlm.nih.gov/pubmed/32499775 http://dx.doi.org/10.3389/fimmu.2020.00755 |
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author | Zhang, Jing Hu, Xiaoxi Dong, Xiaojie Chen, Wensheng Zhang, Lingling Chang, Yan Wu, Yujing Wei, Wei |
author_facet | Zhang, Jing Hu, Xiaoxi Dong, Xiaojie Chen, Wensheng Zhang, Lingling Chang, Yan Wu, Yujing Wei, Wei |
author_sort | Zhang, Jing |
collection | PubMed |
description | Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and T cell hyper-activation. Emerging evidence has shown that the stimulation of immunoglobulin D (IgD) induces T cell activation and may contribute to disease pathogenesis. In this study, the sIgD concentrations were positively associated with disease activity score in 28 joints (DAS28) and anti-cyclic citrullinated peptide (anti-CCP) in RA. We demonstrated that IgD-Fc-Ig (composed of human IgD Fc domain and IgG(1) Fc domain, obtained through prokaryotic protein expression and chromatography purification) effectively inhibited the activation and proliferation of T cells in healthy controls and PBMCs in RA patients stimulated by IgD, recovered the Th17/Treg cell subset balance, and downregulated p-Lck and p-ZAP70 expression. Moreover, in vivo, IgD-Fc-Ig decreased the swollen joint counts and arthritis indices in mice with collagen-induced arthritis (CIA), and ameliorated histopathological changes in joint and spleen tissue. It also downregulated thymocyte proliferation and reduced the percentage of helper T cells (Th) and CD154(+) T cells, reversed the imbalance of Th1/Th2 and Th17/Treg cell subsets, reduced cytokine and chemokine levels, and inhibited p-Lck and p-ZAP70 expression. Our data suggest that IgD-Fc-Ig fusion protein regulates T cell activity in RA. These findings have potential implications for IgD-targeted strategies to treat IgD-associated RA. |
format | Online Article Text |
id | pubmed-7243948 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72439482020-06-03 Regulation of T Cell Activities in Rheumatoid Arthritis by the Novel Fusion Protein IgD-Fc-Ig Zhang, Jing Hu, Xiaoxi Dong, Xiaojie Chen, Wensheng Zhang, Lingling Chang, Yan Wu, Yujing Wei, Wei Front Immunol Immunology Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and T cell hyper-activation. Emerging evidence has shown that the stimulation of immunoglobulin D (IgD) induces T cell activation and may contribute to disease pathogenesis. In this study, the sIgD concentrations were positively associated with disease activity score in 28 joints (DAS28) and anti-cyclic citrullinated peptide (anti-CCP) in RA. We demonstrated that IgD-Fc-Ig (composed of human IgD Fc domain and IgG(1) Fc domain, obtained through prokaryotic protein expression and chromatography purification) effectively inhibited the activation and proliferation of T cells in healthy controls and PBMCs in RA patients stimulated by IgD, recovered the Th17/Treg cell subset balance, and downregulated p-Lck and p-ZAP70 expression. Moreover, in vivo, IgD-Fc-Ig decreased the swollen joint counts and arthritis indices in mice with collagen-induced arthritis (CIA), and ameliorated histopathological changes in joint and spleen tissue. It also downregulated thymocyte proliferation and reduced the percentage of helper T cells (Th) and CD154(+) T cells, reversed the imbalance of Th1/Th2 and Th17/Treg cell subsets, reduced cytokine and chemokine levels, and inhibited p-Lck and p-ZAP70 expression. Our data suggest that IgD-Fc-Ig fusion protein regulates T cell activity in RA. These findings have potential implications for IgD-targeted strategies to treat IgD-associated RA. Frontiers Media S.A. 2020-05-15 /pmc/articles/PMC7243948/ /pubmed/32499775 http://dx.doi.org/10.3389/fimmu.2020.00755 Text en Copyright © 2020 Zhang, Hu, Dong, Chen, Zhang, Chang, Wu and Wei. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Zhang, Jing Hu, Xiaoxi Dong, Xiaojie Chen, Wensheng Zhang, Lingling Chang, Yan Wu, Yujing Wei, Wei Regulation of T Cell Activities in Rheumatoid Arthritis by the Novel Fusion Protein IgD-Fc-Ig |
title | Regulation of T Cell Activities in Rheumatoid Arthritis by the Novel Fusion Protein IgD-Fc-Ig |
title_full | Regulation of T Cell Activities in Rheumatoid Arthritis by the Novel Fusion Protein IgD-Fc-Ig |
title_fullStr | Regulation of T Cell Activities in Rheumatoid Arthritis by the Novel Fusion Protein IgD-Fc-Ig |
title_full_unstemmed | Regulation of T Cell Activities in Rheumatoid Arthritis by the Novel Fusion Protein IgD-Fc-Ig |
title_short | Regulation of T Cell Activities in Rheumatoid Arthritis by the Novel Fusion Protein IgD-Fc-Ig |
title_sort | regulation of t cell activities in rheumatoid arthritis by the novel fusion protein igd-fc-ig |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243948/ https://www.ncbi.nlm.nih.gov/pubmed/32499775 http://dx.doi.org/10.3389/fimmu.2020.00755 |
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