Mucosal-associated invariant T cells in patients with axial spondyloarthritis

Rienk Gerben van der Meer; Anneke Spoorenberg; Elisabeth Brouwer; Berber Doornbos-van der Meer; Annemieke M H Boots; Suzanne Arends; Wayel H Abdulahad

doi:10.3389/fimmu.2023.1128270

Mucosal-associated invariant T cells in patients with axial spondyloarthritis

Front Immunol. 2023 Mar 10:14:1128270. doi: 10.3389/fimmu.2023.1128270. eCollection 2023.

Authors

Rienk Gerben van der Meer¹, Anneke Spoorenberg¹, Elisabeth Brouwer¹, Berber Doornbos-van der Meer¹, Annemieke M H Boots¹, Suzanne Arends¹, Wayel H Abdulahad^{1

2}

Affiliations

¹ Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
² Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Abstract

Background: Several studies implicate Th17-cells and its cytokine (IL-17) in disease pathogenesis of spondyloarthritis (SpA), with available evidence supporting a pathogenic role of CD8+ T-cells. However, data on the involvement of CD8+ mucosal-associated invariant T-cells (MAIT) and their phenotypic characterization and inflammatory function including IL-17 and Granzyme A production in a homogenous population of SpA-patients with primarily axial disease (axSpA) are lacking.

Objectives: Quantify and characterize the phenotype and function of circulating CD8+MAIT-cells in axSpA-patients with primarily axial disease.

Methods: Blood samples were obtained from 41 axSpA-patients and 30 age- and sex-matched healthy controls (HC). Numbers and percentages of MAIT-cells (defined as CD3⁺CD8⁺CD161^highTCR_Vα7.2 ⁺) were determined, and production of IL-17 and Granzyme A (GrzA) by MAIT-cells were examined by flow cytometry upon in vitro stimulation. Serum IgG specific for CMV was measured by ELISA.

Results: No significant differences in numbers and percentages of circulating MAIT-cells were found between axSpA-patients and HCr zijn meer resultaten de centrale memory CD8 T cellen. cellen van patirculating MAIT cells.. Further phenotypic analysis revealed a significant decrease in numbers of central memory MAIT-cells of axSpA-patients compared to HC. The decrease in central memory MAIT-cells in axSpA patients was not attributed to an alteration in CD8 T-cell numbers, but correlated inversely with serum CMV-IgG titers. Production of IL-17 by MAIT-cells was comparable between axSpA-patients and HC, whereas a significant decrease in the production of GrzA by MAIT-cells from axSpA-patients was observed.

Conclusions: The decrease in cytotoxic capability of circulating MAIT-cells in axSpA-patients might implicate that these cell types migrate to the inflamed tissue and therefore associate with the axial disease pathogenesis.

Keywords: Granzyme A; MAIT cells; axial spondyloarthritis; immunology; pathogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Axial Spondyloarthritis*
Cytomegalovirus Infections*
Granzymes
Humans
Immunoglobulin G
Interleukin-17
Mucosal-Associated Invariant T Cells*

Substances

Granzymes
Interleukin-17
Immunoglobulin G

Grants and funding

This research project was supported by an unrestricted grant from Janssen. Janssen had no role in the design, conduct, interpretation, or publication of this study.