Characterization of Blood Mucosal Associated Invariant T ( MAIT ) cells in Axial Spondyloarthritis and of resident MAITs from control axial enthesis

Nicolas Rosine (1) , Hannah Rowe (2) , Surya Koturan (1) , Hanane Yahia‐cherbal (1) , Claire Leloup (1) , Abdulla Watad (2) , Francis Berenbaum (3, 4, 5) , Jeremie Sellam (3, 4, 5) , Maxime Dougados (1, 6, 5) , Vishukumar Aimanianda (7) , Richard Cuthbert (2) , Charlie Bridgewood (2) , Darren Newton (2, 8) , Elisabetta Bianchi (1) , Lars Rogge (9) , Dennis Mcgonagle (2) , Corinne Miceli‐richard (6, 1)

1 Immunorégulation - Immunoregulation
2 University of Leeds
3 SU - Sorbonne Université
4 CHU Saint-Antoine [AP-HP]
5 INSERM - Institut National de la Santé et de la Recherche Médicale
6 Hôpital Cochin [AP-HP]
7 Mycologie moléculaire - Molecular Mycology
8 St James's University Hospital
9 IP - Institut Pasteur [Paris]

Objectives The importance of IL-17A in the pathogenesis of Axial Spondyloarthritis (AxSpA) has been demonstrated by the success of IL-17A blockade. However, the nature of the cell populations producing this important pro-inflammatory cytokine remains poorly defined. Accordingly, we characterized major IL-17A-producing blood cell populations in AxSpA, with reference to entheseal biology, with a focus on mucosal associated invariant T-cells, (MAITs) a population known to be capable of producing IL-17. Methods IL-17A production from 5 sorted peripheral blood cell populations, namely MAITs, γδ T-cells, CD4+T-cells, CD8+T-cells and neutrophils was evaluated pre- and post-stimulation with PMA, the calcium ionophore A23187 and β1,3 glucan. IL-17A transcript and protein expression were determined using nCounter Technology and ultra-sensitive SimoA technology, respectively. MAITs from control human axial entheses (n=5) were further characterized by flow cytometric immunophenotyping, qPCR and IL-17 production assessed following stimulation. Results In blood, on a per cell basis, MAIT cells produced the highest amount of IL-17A compared to CD4+ (p <0.01), CD8+ (p <0.0001) and γδ T-cells (p <0.0001). IL-17A was not produced by neutrophils. Gene expression analysis also showed significantly higher IL17A and IL23R expression in MAIT cells. Stimulation of blood MAIT cells with αCD3/CD28 and IL-7 and/or IL-18 induced strong expression of IL17F. MAITs were present in the normal enthesis and showed elevated AHR, JAK1, STAT4 and TGFB1 transcript expression with inducible IL-17A protein. IL-18 protein expression was evident in spinal enthesis digests. Conclusion Both blood MAITs and resident MAITs in axial entheses contribute to IL-17 production and may play important roles in AxSpA pathogenesis.

Mots clés: IL-17A; IL-17F; IL-17 producing cells; axial spondyloarthritis; MAITs

Domaines: Immunologie

Nicolas Rosine, Hannah Rowe, Surya Koturan, Hanane Yahia‐cherbal, Claire Leloup, et al.. Characterization of Blood Mucosal Associated Invariant T ( MAIT ) cells in Axial Spondyloarthritis and of resident MAITs from control axial enthesis. Arthritis & rheumatology, 2022, ⟨10.1002/art.42090⟩. ⟨pasteur-03670096⟩