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Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF-driven spondyloarthritis

Koen Venken (UGent) , Matthias Jarlborg (UGent) , Tine Decruy (UGent) , Céline Mortier (UGent) , Carolien Vlieghe (UGent) , Elisabeth Gilis (UGent) , Ann-Sophie De Craemer (UGent) , Julie Coudenys (UGent) , Isabelle Cambré (UGent) , Devan Fleury, et al.
(2023) ANNALS OF THE RHEUMATIC DISEASES. 82(8). p.1076-1090
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Abstract
Objectives: Gut and joint inflammation commonly co-occur in spondyloarthritis (SpA) which strongly restricts therapeutic modalities. The immunobiology underlying differences between gut and joint immune regulation, however, is poorly understood. We therefore assessed the immunoregulatory role of CD4+FOXP3+ regulatory T (Treg) cells in a model of Crohn's-like ileitis and concomitant arthritis. Methods: RNA-sequencing and flow cytometry was performed on inflamed gut and joint samples and tissue-derived Tregs from tumour necrosis factor (TNF)∆ARE mice. In situ hybridisation of TNF and its receptors (TNFR) was applied to human SpA gut biopsies. Soluble TNFR (sTNFR) levels were measured in serum of mice and patients with SpA and controls. Treg function was explored by in vitro cocultures and in vivo by conditional Treg depletion. Results: Chronic TNF exposure induced several TNF superfamily (TNFSF) members (4-1BBL, TWEAK and TRAIL) in synovium and ileum in a site-specific manner. Elevated TNFR2 messenger RNA levels were noted in TNF∆ARE/+ mice leading to increased sTNFR2 release. Likewise, sTNFR2 levels were higher in patients with SpA with gut inflammation and distinct from inflammatory and healthy controls. Tregs accumulated at both gut and joints of TNF∆ARE mice, yet their TNFR2 expression and suppressive function was significantly lower in synovium versus ileum. In line herewith, synovial and intestinal Tregs displayed a distinct transcriptional profile with tissue-restricted TNFSF receptor and p38MAPK gene expression. Conclusions: These data point to profound differences in immune-regulation between Crohn's ileitis and peripheral arthritis. Whereas Tregs control ileitis they fail to dampen joint inflammation. Synovial resident Tregs are particularly maladapted to chronic TNF exposure.
Keywords
experimental, arthritis, T-lymphocyte subsets, spondyloarthritis, TUMOR-NECROSIS-FACTOR, PATHWAYS, EFFECTOR

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Citation

Please use this url to cite or link to this publication:

MLA
Venken, Koen, et al. “Distinct Immune Modulatory Roles of Regulatory T Cells in Gut versus Joint Inflammation in TNF-Driven Spondyloarthritis.” ANNALS OF THE RHEUMATIC DISEASES, vol. 82, no. 8, 2023, pp. 1076–90, doi:10.1136/ard-2022-223757.
APA
Venken, K., Jarlborg, M., Decruy, T., Mortier, C., Vlieghe, C., Gilis, E., … Elewaut, D. (2023). Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF-driven spondyloarthritis. ANNALS OF THE RHEUMATIC DISEASES, 82(8), 1076–1090. https://doi.org/10.1136/ard-2022-223757
Chicago author-date
Venken, Koen, Matthias Jarlborg, Tine Decruy, Céline Mortier, Carolien Vlieghe, Elisabeth Gilis, Ann-Sophie De Craemer, et al. 2023. “Distinct Immune Modulatory Roles of Regulatory T Cells in Gut versus Joint Inflammation in TNF-Driven Spondyloarthritis.” ANNALS OF THE RHEUMATIC DISEASES 82 (8): 1076–90. https://doi.org/10.1136/ard-2022-223757.
Chicago author-date (all authors)
Venken, Koen, Matthias Jarlborg, Tine Decruy, Céline Mortier, Carolien Vlieghe, Elisabeth Gilis, Ann-Sophie De Craemer, Julie Coudenys, Isabelle Cambré, Devan Fleury, Alexander Klimowicz, Filip Van den Bosch, Anne Hoorens, Triana Lobatón Ortega, Sytze de Roock, Tim Sparwasser, Gerald Nabozny, Peggy Jacques, and Dirk Elewaut. 2023. “Distinct Immune Modulatory Roles of Regulatory T Cells in Gut versus Joint Inflammation in TNF-Driven Spondyloarthritis.” ANNALS OF THE RHEUMATIC DISEASES 82 (8): 1076–1090. doi:10.1136/ard-2022-223757.
Vancouver
1.
Venken K, Jarlborg M, Decruy T, Mortier C, Vlieghe C, Gilis E, et al. Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF-driven spondyloarthritis. ANNALS OF THE RHEUMATIC DISEASES. 2023;82(8):1076–90.
IEEE
[1]
K. Venken et al., “Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF-driven spondyloarthritis,” ANNALS OF THE RHEUMATIC DISEASES, vol. 82, no. 8, pp. 1076–1090, 2023.
@article{01H1462YX4Y72KMAM66N6AEG8W,
  abstract     = {{Objectives: Gut and joint inflammation commonly co-occur in spondyloarthritis (SpA) which strongly restricts therapeutic modalities. The immunobiology underlying differences between gut and joint immune regulation, however, is poorly understood. We therefore assessed the immunoregulatory role of CD4+FOXP3+ regulatory T (Treg) cells in a model of Crohn's-like ileitis and concomitant arthritis.
Methods: RNA-sequencing and flow cytometry was performed on inflamed gut and joint samples and tissue-derived Tregs from tumour necrosis factor (TNF)∆ARE mice. In situ hybridisation of TNF and its receptors (TNFR) was applied to human SpA gut biopsies. Soluble TNFR (sTNFR) levels were measured in serum of mice and patients with SpA and controls. Treg function was explored by in vitro cocultures and in vivo by conditional Treg depletion.
Results: Chronic TNF exposure induced several TNF superfamily (TNFSF) members (4-1BBL, TWEAK and TRAIL) in synovium and ileum in a site-specific manner. Elevated TNFR2 messenger RNA levels were noted in TNF∆ARE/+ mice leading to increased sTNFR2 release. Likewise, sTNFR2 levels were higher in patients with SpA with gut inflammation and distinct from inflammatory and healthy controls. Tregs accumulated at both gut and joints of TNF∆ARE mice, yet their TNFR2 expression and suppressive function was significantly lower in synovium versus ileum. In line herewith, synovial and intestinal Tregs displayed a distinct transcriptional profile with tissue-restricted TNFSF receptor and p38MAPK gene expression.
Conclusions: These data point to profound differences in immune-regulation between Crohn's ileitis and peripheral arthritis. Whereas Tregs control ileitis they fail to dampen joint inflammation. Synovial resident Tregs are particularly maladapted to chronic TNF exposure.}},
  author       = {{Venken, Koen and Jarlborg, Matthias and Decruy, Tine and Mortier, Céline and Vlieghe, Carolien and Gilis, Elisabeth and De Craemer, Ann-Sophie and Coudenys, Julie and Cambré, Isabelle and Fleury, Devan and Klimowicz, Alexander and Van den Bosch, Filip and Hoorens, Anne and Lobatón Ortega, Triana and de Roock, Sytze and Sparwasser, Tim and Nabozny, Gerald and Jacques, Peggy and Elewaut, Dirk}},
  issn         = {{0003-4967}},
  journal      = {{ANNALS OF THE RHEUMATIC DISEASES}},
  keywords     = {{experimental,arthritis,T-lymphocyte subsets,spondyloarthritis,TUMOR-NECROSIS-FACTOR,PATHWAYS,EFFECTOR}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1076--1090}},
  title        = {{Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF-driven spondyloarthritis}},
  url          = {{http://doi.org/10.1136/ard-2022-223757}},
  volume       = {{82}},
  year         = {{2023}},
}

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