ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1005

Tendon T-cell Interactions as Drivers of Chronicity in Spondyloarthritis

Emma Garcia-Melchor 1, Giacomo Cafaro 1, Hanna Johnsson1, Lindsay Crowe 2, Michael McLean 2, James Reilly 2, Iain McInnes 3, Moeed Akbar 2 and Neal Millar 3, 1University of Glasgow, Glasgow, United Kingdom, 2University of Glasgow, Glasgow, 3Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, United Kingdom

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: , ,

Session Information

Date: Monday, November 11, 2019

Title: Spondyloarthritis Including Psoriatic Arthritis – Basic Science Poster

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Emerging evidence supports the concept that stromal cell functions extend beyond maintenance of tissue architecture, exerting a key role in choreographing immune responses and thereby defining disease persistence. Accordingly, as enthesitis is a hallmark of spondyloarthropaties (SpA), we propose an interplay between tendon stromal cells (tenocytes) and the adaptive immune system (T cells) in the development of a chronic inflammatory response in SpA. 

We aimed to assess the effect of tendon stromal cells (tenocytes) on T cell migration and activation and the impact of these activated T cells on the stroma.

Methods: Tenocytes were explanted from tissue obtained from anterior cruciate ligament (ACL) reconstructions. The effect of damage on tenocytes after stimulation with conditioned media from tendon explants or IL-1ß was evaluated by qPCR. A transwell membrane system was used to test the impact of conditioned media from tenocytes on T cell migration. T cells and tenocytes were co-cultured with or without the presence of a transwell membrane to quantify T cell activation (CD69 by FACS and IFN-γ by ELISA). Changes in gene expression on tenocytes after co-culture with activated T cells were analysed by qPCR.

Results: In the presence of damage, tenocytes upregulated inflammatory mediators (IL-6, COX2), chemokines (CCL2, CCL5, CXCL10, CXCL12) and adhesion molecules (ICAM-1). Conditioned media, particularly after stimulation with IL-1ß, from tenocytes induced T cell migration. Co-cultures of tenocytes and T cells resulted in activation of T cells that was contact dependant. In turn, these activated T cells upregulated the production of inflammatory mediators in tenocytes and increased the COL3/COL1 ratio.

Conclusion: Our results support a role of the tendon stromal compartment in the development and maintenance of an inflammatory response in SpA. Following damage, tendon stromal cells are able to induce the recruitment of T cells, that once enter the tissue interact with the stroma and get further activated. These activated T cells promote an upregulation of inflammatory cytokines and chemokines from the stromal compartment, creating a positive feedback loop that amplifies and maintains this inflammatory response.


ACR 2019 abstract picture

Proposed mechanisms driving T cell/stromal tendon activation in SpA

Disclosure: E. Garcia-Melchor, None; G. Cafaro, None; H. Johnsson, None; L. Crowe, None; M. McLean, None; J. Reilly, None; I. McInnes, Abbott, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche., 2, 8, Abbvie, 5, AbbVie, 2, 5, 8, Amgen, 2, 5, 8, Astra Zeneca, 2, 5, AstraZeneca, 5, BI, 2, 5, BMS, 2, 5, 8, Boehringer Ingelheim, 5, Celgene, 2, 5, 8, Eli Lilly, 2, 5, 8, Janssen, 2, 5, 8, Leo, 5, Lilly, 5, Novartis, 2, 5, 8, Pfizer, 2, 5, 8, UCB, 2, 5, 8; M. Akbar, None; N. Millar, Novartis, 2, 5, 8.

To cite this abstract in AMA style:

Garcia-Melchor E, Cafaro G, Johnsson H, Crowe L, McLean M, Reilly J, McInnes I, Akbar M, Millar N. Tendon T-cell Interactions as Drivers of Chronicity in Spondyloarthritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/tendon-t-cell-interactions-as-drivers-of-chronicity-in-spondyloarthritis/. Accessed .

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/tendon-t-cell-interactions-as-drivers-of-chronicity-in-spondyloarthritis/