Gut Inflammation in axial Spondyloarthritis patients is characterized by a marked Type 17 skewed mucosal Innate-like T cell signature

• Published in: Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2023-11, Vol.75 (11), p.1969-1982
• Main Authors: Mortier, Céline, Quintelier, Katrien, De Craemer, Ann-Sophie, Renson, Thomas, Deroo, Liselotte, Dumas, Emilie, Verheugen, Eveline, Coudenys, Julie, Decruy, Tine, Lukasik, Zuzanna, Van Gassen, Sofie, Saeys, Yvan, Hoorens, Anne, Lobatón, Triana, Van den Bosch, Filip, Van de Wiele, Tom, Venken, Koen, Elewaut, Dirk
• Format: Article
• Language: English
• Subjects: Ankylosing spondylitis; Arthritis; Blood; Cluster analysis; Clustering; Digestive system; Flow cytometry; Gastrointestinal tract; Health risks; Inflammation; Inflammatory diseases; Intestine; Invariants; Lamina propria; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Mucosa; Natural killer cells; Peripheral blood mononuclear cells; Rheumatic diseases; Risk factors; T cell receptors
• ISSN: 2326-5191; 2326-5205
• DOI: 10.1002/art.42627

SpA patients often present with microscopic signs of gut inflammation, a risk factor for progressive disease. We investigated whether mucosal innate-like T-cells are involved in dysregulated interleukin (IL)-23/IL-17 responses in the gut-joint axis in SpA. Ileal and colonic intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL), and paired peripheral blood mononuclear cells (PBMC), were isolated from treatment-naive non-radiographic axial (nr-ax)SpA patients with (n=11) and without (n=14) microscopic gut inflammation, and healthy controls (n=15), undergoing ileocolonoscopy. Presence of gut inflammation was assessed histopathologically. Immunophenotyping of innate-like T-cells and conventional T-cells was performed using intracellular flow cytometry. Unsupervised clustering analysis was done by FlowSOM technology. Serum IL-17A levels were measured via Luminex. Microscopic gut inflammation in nr-axSpA was characterized by increased ileal intraepithelial γδ-hi-T cells. γδ-hi T cells were also increased in PBMC of nr-axSpA patients versus healthy controls, and were strongly associated with ASDAS. The abundance of mucosal associated invariant T (MAIT)-cells and invariant natural killer T (iNKT)-cells was unaltered. Innate-like T-cells in the inflamed gut showed increased RORγt, IL-17A and IL-22 levels with loss of Tbet, a signature that was less pronounced in conventional T-cells. Presence of gut inflammation was associated with higher serum IL-17A levels. In patients treated with TNF blockade, the proportion of γδ-hi cells and RORγt expression in blood was completely restored. Intestinal innate-like T-cells display marked type 17 skewing in the inflamed gut mucosa of nr-axSpA patients. γδ-hi T cells are linked to intestinal inflammation and disease activity in SpA. This article is protected by copyright. All rights reserved.