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Clin Exp Immunol. 2017 Dec;190(3):384-393. doi: 10.1111/cei.13025. Epub 2017 Sep 21.

Rheumatoid arthritis fibroblast-like synoviocytes co-cultured with PBMC increased peripheral CD4+ CXCR5+ ICOS+ T cell numbers.

Author information

1
Department of Immunology, College of Basic Medical Science, Dalian Medical University, Liaoning.
2
Department of Rheumatology and Immunology, Dalian Municipal Central Hospital, Dalian.
3
Department of Rheumatology and Immunology, The Second Affiliated Hospital of Dalian Medical University, Liaoning, China.

Abstract

'Circulating' T follicular helper cells (Tfh), characterized by their surface phenotypes CD4+ chemokine receptor 5 (CXCR5)+ inducible co-stimulatory molecule (ICOS)+ , have been identified as the CD4+ T cell subset specialized in supporting the activation, expansion and differentiation of B cells. Fibroblast-like synoviocytes (FLS) are critical in promoting inflammation and cartilage destruction in rheumatoid arthritis (RA), and the interaction between FLS and T cells is considered to facilitate FLS activation and T cell recruitment. However, it remains unknown whether RA-FLS co-cultured with activated peripheral blood mononuclear cells (PBMC) has immunoregulatory effects on peripheral Tfh. In the present study, we co-cultured RA-FLS with or without anti-CD3/CD28-stimulated PBMC. The results showed that RA-FLS co-cultured with stimulated PBMC could increase the numbers of CD4+ CXCR5+ ICOS+ T cells of RA PBMC possibly via the production of interleukin (IL)-6, a critical cytokine involved in the differentiation of Tfh cells. We also observed increased reactive oxygen species (ROS) levels in the co-culture system of RA-FLS and PBMC. The percentage of CD4+ CXCR5+ ICOS+ T cells was decreased when ROS production was inhibited by N-acetyl-L-cysteine (NAC), a specific inhibitor which can decrease ROS production. In addition, we showed that the higher levels of tumour necrosis factor (TNF)-α and IL-1β in the co-culture system and the blocking of TNF receptor 2 (TNF-R2) and IL-1β receptor (IL-1βR) both decreased the numbers of CD4+ CXCR5+ ICOS+ T cells. Our study reveals a novel mechanistic insight into how the interaction of RA-FLS and PBMC participates in the RA pathogenesis, and also provides support for the biologicals application for RA.

KEYWORDS:

CD4+CXCR5+ICOS+ T cells; fibroblast-like synoviocytes (FLS); interleukin (IL)-6; reactive oxygen species (ROS); rheumatoid arthritis (RA)

PMID:
28833034
PMCID:
PMC5680054
DOI:
10.1111/cei.13025
[Indexed for MEDLINE]
Free PMC Article

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