CD169+ Monocyte and Regulatory T Cell Subsets Are Associated with Disease Activity in Rheumatoid Arthritis

Amanda J. Eakin, Tahanver Ahmed, Cathy M. McGeough, Stephen Drain, H. Denis Alexander, Gary D. Wright, Philip V. Gardiner, Dawn Small, Anthony J. Bjourson, David S. Gibson

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Abstract

Disease activity in rheumatoid arthritis (RA) is influenced by activation of circulating and synovial immune cells. Regulatory T cells (Tregs) and monocytes are key cells that drive inflammation in RA. This study investigated if a relationship exists between disease activity in RA and circulating Treg and monocyte numbers and phenotypes. A potential sialic acid (Sia) mediated link between Tregs and monocytes was also probed in vitro. Peripheral blood mononuclear cells (PBMCs) were isolated from RA patient (n = 62) and healthy control (n = 21) blood using density gradient separation. Flow cytometry was used to count and phenotype Treg and monocyte subsets, and to sort healthy control Tregs for Sia cell culture experiments. The effects of Sia on activated Treg FoxP3 and NFκB expression was assessed by flow cytometry and concentrations of secreted TNFα, IL-10 and IFNγ determined by ELISA. High disease activity RA patients who were unresponsive to disease modifying anti-rheumatic drugs (n = 31), have significantly lower relative numbers (percentages) of CD4+CD25+CD127 Tregs (p < 0.01) and memory CD45RAFoxP3+ Tregs (p < 0.01), compared to low disease activity responders (n = 24). Relative numbers of non-classical CD169+ monocytes are associated with disease activity in RA (p = 0.012). Sia reduced Treg expression of FoxP3, NFκB and cytokines in vitro. A strong association has been identified between non-classical CD169+ monocytes and post-treatment disease activity in RA. This study also indicates that Sia can reduce Treg activation and cytokine release. We postulate that such a reduction could be mediated by interaction with sialyted proteins captured by CD169+ monocytes.

Original languageEnglish
Article number1875
Number of pages16
JournalJournal of Personalized Medicine
Volume12
Issue number11
Early online date9 Nov 2022
DOIs
Publication statusPublished online - 9 Nov 2022

Bibliographical note

Funding Information:
D.S.G. and A.J.E. wish to acknowledge the award of a PhD fellowship from Department for the Economy, Northern Ireland, UK. The Northern Ireland Centre for Stratified Medicine was financed by a grant awarded to Professor A.J. Bjourson under the European Union Regional Development Fund (ERDF) EU Sustainable Competitiveness Programme for Northern Ireland & the Northern Ireland Public Health Agency (HSC R&D).

Publisher Copyright:
© 2022 by the authors.

Keywords

  • rheumatoid arthritis
  • inflammation
  • cytokine
  • regulatory T cell
  • monocyte

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