Effect of Integrin Blockade on Experimental Spondyloarthritis

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2024 Nov 27

PMID 39595563

Authors

Enoch Yau

Melissa Lim

Zoya Qaiyum

Shaghayegh Foroozan Boroojeni

Michael Tang

Addison Pacheco

Fataneh Tavasolian

Robert D Inman

Affiliations

Soon will be listed here.

Abstract

Spondyloarthritis (SpA) describes a group of diseases characterized by chronic inflammation in the spine and peripheral joints. While pathogenesis is still unclear, proinflammatory gut-derived immune cells have been identified in the joints of SpA patients. We previously identified an enriched population of integrin-expressing cells in the joints of SpA patients. Entry of gut-derived cells into joints may be mediated by these integrins. In the current study, we used the SKG murine model of SpA to study the impact of integrin blockade. Mice were injected with antibodies against the integrin α4β7 or the β7 monomer twice a week. Treatment with antibodies against α4β7 reduced disease severity in curdlan-injected SKG mice, with disease scores being comparable between treatment initiation times. Targeting the β7 monomer led to reduced arthritis severity compared to targeting the α4β7 dimer. Treatment with antibodies against α4β7 or β7 decreased expression of these integrins in CD4+ T cells, with the frequency of αE+β7+ T cells in the spleen and lymph nodes correlating with disease severity. In summary, we showed that integrin blockade showed potential for ameliorating disease in a murine model of SpA, lending support for further studies testing integrin blockade in SpA.

References

Reveille J . Genetics of spondyloarthritis--beyond the MHC. Nat Rev Rheumatol. 2012; 8(5):296-304. DOI: 10.1038/nrrheum.2012.41. View

Ruutu M, Thomas G, Steck R, Degli-Esposti M, Zinkernagel M, Alexander K . β-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice. Arthritis Rheum. 2012; 64(7):2211-22. DOI: 10.1002/art.34423. View

Holm T, Poulsen S, Markholst H, Reedtz-Runge S . Pharmacological Evaluation of the SCID T Cell Transfer Model of Colitis: As a Model of Crohn's Disease. Int J Inflam. 2012; 2012:412178. PMC: 3328770. DOI: 10.1155/2012/412178. View

Orlando A, Orlando R, Ciccia F, Renna S, Rizzo A, Cottone M . Clinical benefit of vedolizumab on articular manifestations in patients with active spondyloarthritis associated with inflammatory bowel disease. Ann Rheum Dis. 2017; 76(9):e31. DOI: 10.1136/annrheumdis-2016-211011. View

Chang M, Levescot A, Nelson-Maney N, Blaustein R, Winden K, Morris A . Arthritis flares mediated by tissue-resident memory T cells in the joint. Cell Rep. 2021; 37(4):109902. PMC: 8561718. DOI: 10.1016/j.celrep.2021.109902. View

Qiu Z, Sheridan B . Isolating Lymphocytes from the Mouse Small Intestinal Immune System. J Vis Exp. 2018; (132). PMC: 5931411. DOI: 10.3791/57281. View

Gill T, Rosenbaum J . Putative Pathobionts in HLA-B27-Associated Spondyloarthropathy. Front Immunol. 2021; 11:586494. PMC: 7848169. DOI: 10.3389/fimmu.2020.586494. View

Elewaut D, de Keyser F, Van den Bosch F, Lazarovits A, De Vos M, Cuvelier C . Enrichment of T cells carrying beta7 integrins in inflamed synovial tissue from patients with early spondyloarthropathy, compared to rheumatoid arthritis. J Rheumatol. 1998; 25(10):1932-7. View

Bishu S, El Zaatari M, Hayashi A, Hou G, Bowers N, Kinnucan J . CD4+ Tissue-resident Memory T Cells Expand and Are a Major Source of Mucosal Tumour Necrosis Factor α in Active Crohn's Disease. J Crohns Colitis. 2019; 13(7):905-915. PMC: 6939878. DOI: 10.1093/ecco-jcc/jjz010. View

10.

Varkas G, Thevissen K, De Brabanter G, Van Praet L, Czul-Gurdian F, Cypers H . An induction or flare of arthritis and/or sacroiliitis by vedolizumab in inflammatory bowel disease: a case series. Ann Rheum Dis. 2016; 76(5):878-881. DOI: 10.1136/annrheumdis-2016-210233. View

11.

Wendling D, Sondag M, Verhoeven F, Vuitton L, Koch S, Prati C . Arthritis occurrence or reactivation under Vedolizumab treatment for inflammatory bowel disease. A four cases report. Joint Bone Spine. 2017; 85(2):255-256. DOI: 10.1016/j.jbspin.2017.01.012. View

12.

Arihiro S, Ohtani H, Suzuki M, Murata M, Ejima C, Oki M . Differential expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in ulcerative colitis and Crohn's disease. Pathol Int. 2002; 52(5-6):367-74. DOI: 10.1046/j.1440-1827.2002.01365.x. View

13.

Min H, Choi J, Lee S, Lee A, Min B, Cho M . Vitronectin-derived bioactive peptide prevents spondyloarthritis by modulating Th17/Treg imbalance in mice with curdlan-induced spondyloarthritis. PLoS One. 2022; 17(1):e0262183. PMC: 8730421. DOI: 10.1371/journal.pone.0262183. View

14.

Ellinghaus D, Jostins L, Spain S, Cortes A, Bethune J, Han B . Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. Nat Genet. 2016; 48(5):510-8. PMC: 4848113. DOI: 10.1038/ng.3528. View

15.

Ben-Horin S, Bank I . The role of very late antigen-1 in immune-mediated inflammation. Clin Immunol. 2004; 113(2):119-29. DOI: 10.1016/j.clim.2004.06.007. View

16.

Salmi M, Rajala P, Jalkanen S . Homing of mucosal leukocytes to joints. Distinct endothelial ligands in synovium mediate leukocyte-subtype specific adhesion. J Clin Invest. 1997; 99(9):2165-72. PMC: 508046. DOI: 10.1172/JCI119389. View

17.

Souza H, Elia C, Spencer J, MacDonald T . Expression of lymphocyte-endothelial receptor-ligand pairs, alpha4beta7/MAdCAM-1 and OX40/OX40 ligand in the colon and jejunum of patients with inflammatory bowel disease. Gut. 1999; 45(6):856-63. PMC: 1727744. DOI: 10.1136/gut.45.6.856. View

18.

Bottois H, Ngollo M, Hammoudi N, Courau T, Bonnereau J, Chardiny V . KLRG1 and CD103 Expressions Define Distinct Intestinal Tissue-Resident Memory CD8 T Cell Subsets Modulated in Crohn's Disease. Front Immunol. 2020; 11:896. PMC: 7235448. DOI: 10.3389/fimmu.2020.00896. View

19.

Harrell M, Iritani B, Ruddell A . Lymph node mapping in the mouse. J Immunol Methods. 2008; 332(1-2):170-4. PMC: 2342937. DOI: 10.1016/j.jim.2007.11.012. View

20.

Qaiyum Z, Tang M, Olivera P, Inman R . Differential Effects of Integrin Blockade on Gut and Sacroiliac Joint Inflammation. J Rheumatol. 2023; 50(8):1090-1092. DOI: 10.3899/jrheum.2022-1272. View