@article{01H3HSG0PR3N00ZJV8ZD2DAQNT,
  abstract     = {{Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.}},
  author       = {{Mortier, Céline and Quintelier, Katrien and De Craemer, Ann-Sophie and Renson, Thomas and Deroo, Liselotte and Dumas, Emilie and Verheugen, Eveline and Coudenys, Julie and Decruy, Tine and Łukasik, Zuzanna and Van Gassen, Sofie and Saeys, Yvan and Hoorens, Anne and Lobatón Ortega, Triana and Van den Bosch, Filip and Van de Wiele, Tom and Venken, Koen and Elewaut, Dirk}},
  issn         = {{2326-5191}},
  journal      = {{ARTHRITIS & RHEUMATOLOGY}},
  keywords     = {{Immunology,Rheumatology,Immunology and Allergy}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1969--1982}},
  publisher    = {{Wiley}},
  title        = {{Gut inflammation in axial spondyloarthritis patients is characterized by a marked type 17 skewed mucosal innate‐like T cell signature}},
  url          = {{http://doi.org/10.1002/art.42627}},
  volume       = {{75}},
  year         = {{2023}},
}

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