Background/Purpose:     Source of IL-17 in human has been mainly attributed to ab T cells, more specifically to the Th17 cells. However, some reports suggest that cells of the innate immune system: γd T cells and NKT cells may be the major contributing IL-17 producing cells in psoriatic arthritis (PsA).  To have a definite answer; here we have studied arrays of IL-17 producing T cell phenotypes in PsA including the Mucosal associated invariant T (MAIT) cells. 

Methods:

•        PBMC and synovial fluid mononuclear cells (SFMC) from age/sex matched active PsA patients (n=15) and normal individuals (n=15) were collected 

•        Patients were not on DMARDS or biologics

•        rIL-23 induced activated IL-17+ T cells were generated and stained as per our earlier reports (Raychaudhuri SP, etal. Mol Cell Biochem. 2012 ;359:419-29 ).

•        Hi-D FACS studies were done to identify the activated memory effector CD11a+CD45RO+IL-17+ T cells. MAIT cells were CD3+Vα7.2TCR+CD161^high, γd T cells were CD3+γdTCR+, ab T cells were CD3+abTCR+, invariant CD1d-restricted natural killer (NK) T cells were CD1d/PBS-57 tetramer+CD3+. The percentages of each cell population and the mean fluorescence intensity (MFI) were analyzed using FlowJo software.                    

Results:

The percentage of IL-17+ CD3+ T cells was far higher in both PBMC (20­­.5 ± 0.5%) and SFMC (43± 0.7% ) in PsA patients  compared to 3± 0.5% in PBMC of healthy persons (p<0.001).

Both PBMC and SFMC in PsA patients demonstrated IL-17+ effector memory T cells (TEM) in the following T cell phenotypes: ab T cells, γd T cells, NKT cells and MAIT cells. The frequency of these CD3+IL-17+ T cells in the PBMC and SFMC in PsA patients are described in the Table-1 (Table 1).  An important observation we noticed that IL-17+ MAIT cell in SFMC were enriched (5%) compared to 1 % in PBMC and they were predominantly CD8+ (~ 90%).

Conclusion:

· In PsA, pathologic CD11a+CD45RO+IL-17+ T cells are comprised of cells of both the innate and acquired immune response:   ab T cells, γd T cells, MAIT cells and NKT cells.  

·  However, compared to the other phenotypes, the dominant (~ 80%) IL-17+T cells in PsA (both in PBMC and SFMC) were conventional T-helper 17 (Th17) CD4+CD11a+CD45RO+abTCR+ T cells (p<0.001%) (Table 1).   

· MHC class-1 association, subclinical colitis and enrichment of Tc17 CD8+/MAIT cells in SFMC in PsA could be of additional pathological significance and needs further evaluation.

Table 1.  IL-17 expression (%) in gated CD3+CD11a+CD45RO+ T cells in different T cell phenotypes in SFMC and PBMC of PsA. αβTCR IL-17+ cells are significantly more than NKT, MAIT and γdTCR, p<0.001.