FRI0355 MUCOSAL ASSOCIATED INVARIANT T-CELLS ARE ENRICHED AT THE HUMAN ENTHESIS AND HAVE A RESIDENT MEMORY PHENOTYPE

Background Mucosal associated invariant T-cells (MAITs) are innate-like T lymphocytes that express a semi-invariant TCR repertoire. They are activated by microbial ligands or cytokines including IL-23 and secrete inflammatory cytokines, including IFNγ and IL-17A. MAIT cells are enriched at mucosal surfaces and have been implicated in the pathogenesis of spondyloarthritis (SpA) (1) and inflammatory bowel disease (IBD). Although the human enthesis is not a mucosal surface it is the primary site of inflammation in SpA which has strong association with IBD. Objectives To investigate if a population of MAITs is present at the normal human enthesis thereby establishing a potential link between gut and joint inflammation. Methods Healthy interspinous ligament and spinous process were harvested from patients undergoing elective surgery for the correction of mechanical spinal defects. Entheseal soft tissue (EST) and peri-entheseal bone (PEB) were separated and cells were harvested by enzymatic and mechanical digestion respectively. The proportion of cells expressing markers consistent with MAITS (CD45+, CD3+, CD161+, TCRVα7.2+) were measured by flow cytometry in EST, PEB and matched blood. Expression of CD69 and CD45RA were examined for phenotypic analysis. Transcript analysis for IL-23/IL-17 axis and immunomodulatory genes was performed on sorted entheseal MAITs and analysed by TaqMan array. Results As a proportion of total T-cells, MAITs were of approximately 3 fold and 2.5 fold greater abundance in EST and PEB respectively in comparison to matched peripheral blood (both p=0.034). MAITs in entheseal tissue had an overwhelming resident memory phenotype (CD69+, CD45RA-) median 53.2% (range 42.4 – 78.6%) in EST and 54.9% (45.2 - 82.1%) in PEB compared to those from blood 17.7 (6.8 – 69.4). MAITs robustly expressed RORC, CCR6 and IL-23R transcript. Compared to conventional entheseal T-cells, MAITs expressed significantly less TGFβ (6-fold, p>0.001) and significantly more IL-23R (29-fold, p=0.004). Conclusion Healthy human entheseal tissue contains an enriched population of MAITs that strongly express IL-23R transcript at a frequency comparable to that reported in the colon (2). The majority of these cells express a resident memory phenotype suggesting that they are a distinct population residing in entheseal tissue. These observations are potentially relevant to SpA pathogenesis and the observed link between SpA and IBD. References [1] Gracey E, Qaiyum Z, Almaghlouth I, Lawson D, Karki S, Avvaru N, et al. IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, which contribute to the Th17-axis in ankylosing spondylitis. Annals of the rheumatic diseases. 2016:annrheumdis-2015-208902. [2] Salou M, Franciszkiewicz K, Lantz O. MAIT cells in infectious diseases. Current opinion in immunology. 2017;48:7-14. Disclosure of Interests Richard Cuthbert: None declared, Qiao Zhou: None declared, Abdulla Watad: None declared, Robert Dunsmuir: None declared, Peter Loughenbury: None declared, Almas Khan: None declared, Peter Millner: None declared, Charlie Bridgewood: None declared, Dennis McGonagle Consultant for: Lilly, Novartis UCB, Speakers bureau: Lilly, Novartis UCB