Mucosal‐associated invariant T cells are reduced and functionally immature in the peripheral blood of primary Sjögren's syndrome patients

Abstract

The frequencies, immunophenotype, and function of mucosal-associated invariant T (MAIT) cells were studied in patients with primary Sjögren syndrome (pSS) and healthy controls. MAIT cells were significantly decreased in the peripheral blood (PB) of patients with pSS. Vα7.2 MAIT cells were detected in the salivary gland tissue from pSS patients, but not in controls, indicating that the reduction of MAIT cells in PB might be due to migration into the target tissue. Furthermore, the residual peripheral blood MAIT cells in pSS patients showed altered immunophenotype and function. While MAIT cells from controls were almost exclusively CD8 and expressed an effector memory immunophenotype, in pSS patients they were enriched in CD4 and naïve subpopulations. Consistently, the functional studies demonstrated that MAIT cells from pSS showed a lower level of activation with reduced expression of CD69 and CD154 (CD40L), and a lower production of TNF and IFN-γ. In summary, our findings demonstrate that MAIT cells were reduced and phenotypically and functionally altered in PB of pSS patients. The altered function of MAIT cells in target tissues from pSS patients may result in dysregulation of mucosal immunity leading to microbial damage of mucosal surfaces and subsequent initiation of autoimmune response.

IL‐17 polarization of MAIT cells is derived from the activation of two different pathways

“…The altered function of MAIT cells in pSS SG might lead to the dysregulation of the local immune responses, triggering autoimmune damage of the glandular tissue and development of sicca symptoms. Although Wang et al showed a lower level of MAIT-cell activation with reduced expression of CD69 and CD154 (CD40L) and a lower production of TNF and IFN-γ, a precise functional characterization of MAIT cells in pSS patients is still missing [1].…”

Mucosal‐associated invariant T cells in autoimmune and immune‐mediated diseases

“…Functional analysis suggested that MAIT cells from pSS patients produced less cytokines, TNF and IFNc, as compared to healthy controls (PMA iono). 49 A second study confirmed the reduction of blood MAIT cells in pSS patients and further showed an enrichment of IL-17 polarized MAIT cells. 50 In vitro stimulation of purified blood MAIT cells from pSS patients with IL-7 and IL-23, two cytokines involved in pSS pathogenesis, enhanced their level of IL-17 mRNA.…”

“…However, this modification might reflect an increased proportion of Vα7.2 + T cells that are not MAIT cells (no MR1‐tetramer staining were performed). Functional analysis suggested that MAIT cells from pSS patients produced less cytokines, TNF and IFNγ, as compared to healthy controls (PMA iono) . A second study confirmed the reduction of blood MAIT cells in pSS patients and further showed an enrichment of IL‐17 polarized MAIT cells .…”

“…Interestingly, while IL‐7 induced upregulation of STAT‐3 and HIF1a transcripts, IL‐23 induced RORc mRNA expression in MAIT cells . Together these studies suggest that altered MAIT cells in pSS patients could participate to the disease through their IL‐17 production …”

“…50 Together these studies suggest that altered MAIT cells in pSS patients could participate to the disease through their IL-17 production. 49,50…”