Functional significance of MAIT cells in psoriatic arthritis

Background: Mucosal-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. Methods: Peripheral 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(+)V alpha 7.2TCR(+)CD161(hi)) 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. Results: MAIT 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. Conclusion: MAIT cells are poly functional; produce multiple cytokines (IL-17A, IFN-gamma, TNF-alpha). 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.