ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • 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
    • Register
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 336

The Additive Inflammatory in Vivo and in Vitro Effects of Thymic Stromal Lymphopoietin (TSLP) and IL-7 in Arthritis Underscore the Therapeutic Rationale for blockade of Their Common Receptor Subunit

M.R. Hillen1,2, S.A.Y. Hartgring1,2, T.R.D.J. Radstake2,3, C.E. Hack1,2, F.P.J.G. Lafeber1 and J.a.G. van Roon1,2, 1Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht, Netherlands, 2Laboratory for Translational Immunology, UMC Utrecht, Utrecht, Netherlands, 3Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Animal models, Dendritic cells, rheumatoid arthritis (RA) and rheumatoid arthritis, T cells

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Session Title: Rheumatoid Arthritis - Animal Models

Session Type: Abstract Submissions (ACR)

Background/Purpose

Interleukin (IL)-7 and thymic stromal lymphopoietin (TSLP) are cytokines that signal through the IL-7Ra subunit and play proinflammatory roles in experimental arthritis and rheumatoid arthritis (RA). IL-7R blockade can potentially block signalling of both cytokines. In this study the potential of IL-7R and TSLPR signalling inhibition as well as simultaneous inhibition was investigated in murine experimental arthritis. In addition, the additive effects of IL-7 and TSLP in human RA in vitro dendritic cell (DC)/T-cell co-cultures were studied.

Methods

Proteoglycan-induced arthritis was induced in wildtype mice (WT) and mice deficient for the TSLP receptor subunit (TSLPR) and mice of both genotypes were treated with anti-IL-7R or PBS. Arthritis severity was assessed and paw lysate and serum were collected for cytokine analyses. CD1c DCs and CD4 T-cells were isolated from blood of RA patients and were co-cultured in presence of IL-7, TSLP or the combination of both cytokines and proliferation and cytokine production were assessed.

Results

Arthritis severity and synovitis were significantly decreased in TSLPR-/- mice treated with anti-IL-7R compared to control mice (Arthritis severity; mean area under the curve ± SEM: 25 ± 5.9 vs. 50.7 ± 6.9; p<0.01). This was associated with strongly reduced radiographic joint damage and osteoclast activity, which were significantly lower in TSLPR-/- mice treated with anti-IL-7R compared to WT mice treated with anti-IL-7R, PBS treated TSLPR-/- mice or PBS treated WT mice (Radiographic joint damage: Mean score ± SEM: 0.1 ± 0.1, 0.6 ± 0.1, 0.3 ± 0.1, 1.4 ± 0.2 respectively; all p<0.001). This was associated with  decreased levels of IL-17, IL-6, IL-1β and CD40L, which were all robustly downregulated by combined blockade of IL-7 and TSLP signalling (all p<0.05). In DC/CD4 T-cell co-cultures from RA patients, TSLP and IL-7 additively increased T-cell proliferation (p<0.01) and production of Th17-associated cytokines (IL-17, IL-22, IL-6; all p<0.05) and T-cell attracting chemokines (all p<0.05).

Conclusion

TSLP and IL-7 additively promote production of Th17-specific and Th17-associated cytokines, linked with enhanced inflammation and immunopathology. As both cytokines signal via the IL-7Ra, these data emphasize the need for drugs that target this subunit to abrogate activity of both ligands and prevent immunopathology in RA.


Disclosure:

M. R. Hillen,
None;

S. A. Y. Hartgring,
None;

T. R. D. J. Radstake,
None;

C. E. Hack,
None;

F. P. J. G. Lafeber,
None;

J. A. G. van Roon,
None.

  • Tweet
  • Email
  • Print
Save to PDF

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-additive-inflammatory-in-vivo-and-in-vitro-effects-of-thymic-stromal-lymphopoietin-tslp-and-il-7-in-arthritis-underscore-the-therapeutic-rationale-for-blockade-of-their-common-receptor-subu/

Advanced Search

Your Favorites

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

ACR Convergence: Where Rheumatology Meets. All Virtual. November 5-9.

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2021 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.
This site uses cookies: Find out more.