Functional significance of MAIT cells in psoriatic arthritis

Abstract

BackgroundMucosal-associated invariant T (MAIT) cells are gaining more relevance for autoimmune diseases because of its (i) innate and adaptive immune response (ii) tissue homing properties (iii) production of IL-17A. These cells are predominantly CD8+ cells, because of its strong association with MHC-I. Tc17 CD8+/MAIT cells likely to have a critical role in psoriatic arthritis (PsA). Herein, we have explored pathological significance of MAIT cell in PsA. MethodsPeripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were collected from age/sex matched (n = 10 for each) PsA, rheumatoid arthritis (RA) and osteoarthritis patients (OA). Hi-D FACS studies were performed: (i) activated memory cells (CD3+CD45RO+) T cells were identified (ii) gating strategies were made to identity the MAIT (CD3+Vα7.2TCR+CD161hi) cells, its phenotype pattern; and functional significance in respect to IL-17A production and responsiveness to human rIL-23. Anti CD3/CD28 ab cocktail was used to activate cells along with rIL-23 to culture and enrich the MAIT cells. The percentages of each cell population and the mean fluorescence intensity (MFI) were analyzed using Flow Jo software. ResultsMAIT cells were enriched in synovial fluid of PsA (4.29 ± 0.82%) compared to PBMC (1.04 ± 0.71). With stimulation, SFMC MAIT cells produced significantly more IL-17A (32.66 ± 4.01%) compared to that of RA (23.93 ± 2.81%, p < 0.05) and OA (5.02 ± 0.16%, p < 0.05). MAIT cells were predominantly CD8+ (>80%). Significant upregulation of IL-23R was noted in synovial fluid MAIT cells of PsA (24.97 ± 2.33%, p < 0.001) and RA (21.93 ± 2.29%, p < 0.001) compared to that of OA (2.13 ± 2.29). This IL-23R was functionally active as evidenced by profound mitotic effect in presence of rIL-23. ConclusionMAIT cells are poly functional; produce multiple cytokines (IL-17A, IFN-γ, TNF-α). Here, we demonstrated synovial fluid MAIT cells as a major source of IL-17A and majority of MAIT cells were CD8+. Functionally active IL-23R on these migrated MAIT cells brings a new dimension. They may not need MR1 associated activation rather lesional IL-23 in the synovium can independently regulate these critical Tc17 CD8+ MAIT cells. Thus, these cells likely to be a part of the IL-23/IL-17A cytokine network and play a critical role in the pathogenesis of PsA.