Journal
FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.1017157
Keywords
Sjogren's syndrome (pSS); MAIT cells; CCR9; CXCR5 T cells; IL-7R alpha (CD127); IL-18R alpha
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Funding
- [17-2-403]
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This study found that the numbers of CD161+ and IL-18R alpha+ MAIT cells were decreased in pSS patients. CCR9 and CXCR5-expressing MAIT cells were significantly higher in pSS patients compared to healthy controls. The expression of IL-7R correlated to several clinical parameters. Treatment with LEF/HCQ inhibited the production of IL-21 by MAIT cells. The study indicates a potential role for MAIT cells in driving pSS immunopathology.
Introduction: Mucosal-associated invariant T (MAIT) cells might play a role in B cell hyperactivity and local inflammation in primary Sjogren's syndrome (pSS), just like previously studied mucosa-associated CCR9+ and CXCR5+ T helper cells. Here, we investigated expression of CCR9, CXCR5, IL-18R and IL-7R on MAIT cells in pSS, and assessed the capacity of DMARDs to inhibit the activity of MAIT cells. Methods: Circulating CD161+ and IL-18R alpha+ TCRV alpha 7.2+ MAIT cells from pSS patients and healthy controls (HC) were assessed using flow cytometry, and expression of CCR9, CXCR5, and IL-7R on MAIT cells was studied. Production of IFN-gamma and IL-21 by MAIT cells was measured upon IL-7 stimulation in the presence of leflunomide (LEF) and hydroxychloroquine (HCQ). Results: The numbers of CD161+ and IL-18R alpha+ MAIT cells were decreased in pSS patients compared to HC. Relative increased percentages of CD4 MAIT cells in pSS patients caused significantly higher CD4/CD8 ratios in MAIT cells. The numbers of CCR9 and CXCR5-expressing MAIT cells were significantly higher in pSS patients. IL-7R expression was higher in CD8 MAIT cells as compared to all CD8 T cells, and changes in IL-7R expression correlated to several clinical parameters. The elevated production of IL-21 by MAIT cells was significantly inhibited by LEF/HCQ treatment. Conclusion: Circulating CD161+ and IL-18R alpha+ MAIT cell numbers are decreased in pSS patients. Given their enriched CCR9/CXCR5 expression this may facilitate migration to inflamed salivary glands known to overexpress CCL25/CXCL13. Given the pivotal role of IL-7 and IL-21 in inflammation in pSS this indicates a potential role for MAIT cells in driving pSS immunopathology.
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