ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 2002

Presence of the MerTK Receptor on Human Synovial Tissue Macrophages Lowers Inflammatory Cytokine Production and Activation of the MerTK+CD206+ Subpopulation Limits the Inflammatory Response of Synovial Fibroblasts

Samuel Finlay1, Stefano Alivernini 2, Aziza Elmesmari 3, Barbara Tolusso 2, Luca Petricca 2, Clara Di Mario 4, Annunziata Capacci 2, Andrew Filer 5, Gianfranco Ferraccioli 2, Iain McInnes 1, Elisa Gremese 2 and Mariola Kurowska-Stolarska 1, 1Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, United Kingdom, 2Division of Rheumatology - Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy, 3Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, Scotland, United Kingdom, 4Institute of Rheumatology - Università Cattolica del Sacro Cuore, Rome, Italy, 5Institute of Inflammation and Ageing College of Medical and Dental Sciences University of Birmingham, Birmingham, United Kingdom

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: fibroblasts and rheumatoid arthritis, macrophages, pathogenesis, rheumatoid arthritis, synovium

  • Tweet
  • Email
  • Print
Session Information

Date: Tuesday, November 12, 2019

Session Title: RA – Etiology & Pathogenesis Poster II

Session Type: Poster Session (Tuesday)

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

Background/Purpose: Background: A substantial proportion of Rheumatoid Arthritis patients do not respond to treatment and only a small proportion achieve sustained disease remission. We showed previously that human synovial tissue macrophages (STMs) are heterogeneous; and a sub-population of CD206+MertK+ positive STMs predominates in RA patients in sustained remission as compared to patients with active RA. Their surface receptors, e.g. MerTK, and distinct transcriptome suggest that they may play a role in re-enforcing joint homeostasis (1). Thus, we hypothesise that activation of CD206+MerTK+ human synovial tissue macrophages contributes to the resolution of inflammation. 

Objectives: We aimed to investigate whether activation of MerTK in STM sub-population promotes an anti-inflammatory environment in the synovium.

Methods: Methods: Using flow cytometric techniques and with a specific antibody panel design (1), STMs from digested RA synovial biopsies were phenotyped and/or harvested for functional studies. The study included patients with active disease and patients in remission (DAS28 ESR< 2.6 and power doppler negative). After excluding all other cell types, macrophages were gated based on the expression of CD64 and CD11b (CD45posCD64posCD11bposHLA-DRpos) (1). Two distinct subpopulations: CD206+MerTK+ and CD206-MerTK- were sorted and cultured on a collagen coated 96-well plate at 1000 cells per well in the presence of with LPS (10ng/ml) ± Gas 6, a MerTK ligand (100ng/ml), for 24h. Cytokine production was measured using a high sensitivity UPLEX assay. To test the role of MerTK expressing macrophages on the activation of synovial fibroblasts, a trans-well membrane coculture system was used. Macrophages were pre-treated with LPS (1ng/ml)  ± MertK inhibitor (UNC1062, 100um-250um) for 4 and 2 hours respectively, and then co-cultured with fibroblasts for 48hours. MMPs production were measured by multiplex.

Results: Results: As previously shown (1), RA patients in sustained remission have a majority CD206+MerTK+ STMs, whilst patients with active RA show an increased number of CD206–MerTK– macrophages.  The percentage of CD206+MerTK+ macrophages negatively correlated with the disease activity score in RA.  Stimulation of FACS-Aria sorted CD206+MerTK+ and CD206–MerTK– macrophages with TLR4 ligand induced a different cytokine pattern:  the CD206–MerTK– macrophages mostly produced TNF, IL-6 and IL-1b while CD206+MerTK+ produced IL-10.  Inhibition of MerTK in macrophages increased the production of MMP1 and MMP3 by synovial fibroblasts in the co-culture system. 

Conclusion: Conclusion: CD206+MERTK+ macrophages, which predominate in RA patients in remission, have Gas6-mediated negative feedback mechanism limiting inflammatory cytokine production and activation of synovial fibroblasts. Thus, Gas6/MerTK pathway in synovial tissue macrophages could drive the resolution of inflammation and synovial tissue homeostasis.

References:

  1. Elmesmari A et al., Synovial tissue of RA patients in remission contains a unique population of regulatory macrophages. Annals of the Rheumatic Diseases, 2017;76 (Suppl2) 138-139.

Disclosure: S. Finlay, None; S. Alivernini, None; A. Elmesmari, None; B. Tolusso, None; L. Petricca, None; C. Di Mario, None; A. Capacci, None; A. Filer, None; G. Ferraccioli, 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; E. Gremese, AbbVie, 5, 8, Abbvie, 5, 8, BMS, 5, 8, Bristol-Myers Squibb, 5, 8, Celgene, 5, 8, Jannsen, 5, 8, Lilly, 5, 8, MSD, 5, 8, Novartis, 5, 8, Pfizer, 5, 8, Sandoz, 5, 8, UCB, 5, 8; M. Kurowska-Stolarska, None.

To cite this abstract in AMA style:

Finlay S, Alivernini S, Elmesmari A, Tolusso B, Petricca L, Di Mario C, Capacci A, Filer A, Ferraccioli G, McInnes I, Gremese E, Kurowska-Stolarska M. Presence of the MerTK Receptor on Human Synovial Tissue Macrophages Lowers Inflammatory Cytokine Production and Activation of the MerTK+CD206+ Subpopulation Limits the Inflammatory Response of Synovial Fibroblasts [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/presence-of-the-mertk-receptor-on-human-synovial-tissue-macrophages-lowers-inflammatory-cytokine-production-and-activation-of-the-mertkcd206-subpopulation-limits-the-inflammatory-response-of-synovia/. Accessed May 26, 2022.
  • Tweet
  • Email
  • Print

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/presence-of-the-mertk-receptor-on-human-synovial-tissue-macrophages-lowers-inflammatory-cytokine-production-and-activation-of-the-mertkcd206-subpopulation-limits-the-inflammatory-response-of-synovia/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2022 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.