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: 1915

Partial Elimination of Intestinal Microbiota Dampens T Helper 17 Cell Differentiation and Established Collagen-Induced Arthritis in Mice

Rebecca Rogier1, Heather Evans-Marin2, Birgitte Walgreen1, Monique M. Helsen1, Liduine van den Bersselaar1, Peter M. van der Kraan1, Fons A.J. van de Loo3, Peter L. van Lent1, Jose U. Scher4, Wim B. van den Berg1, Marije I. Koenders1 and Shahla Abdolahi-Roodsaz1, 1Experimental Rheumatology, Radboud university medical center, Nijmegen, Netherlands, 2Division of Rheumatology, New York University School of Medicine, New York, NY, 3Rheumatology, Radboud university medical center, Nijmegen, Netherlands, 4New York University School of Medicine, New York, NY

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Antibiotics, Arthritis, microbiome and mouse model, T cells

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Date: Monday, November 14, 2016

Session Title: T Cell Biology and Targets in Autoimmune Disease - Poster Session I

Session Type: ACR Poster Session B

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

Background/Purpose: High-throughput sequencing of intestinal microbiota recently revealed that the composition of intestinal microbiota is perturbed in patients with new onset untreated rheumatoid arthritis (RA). In mice, both germ-free condition and administration of oral antibiotics before the onset of arthritis modulate T cell differentiation and attenuate the disease. However, it is not known whether and how modulation of intestinal microbiota after the onset of arthritis may influence the disease. Here, we investigated the involvement of commensal intestinal microbiota in the progression of established arthritis in both T cell-dependent and -independent mouse models.

Methods: Mice with established collagen-induced arthritis (CIA) as the most widely-used T cell-dependent model of RA, as well as mice with K/BxN serum-transfer arthritis as a T cell-independent model were treated orally with a cocktail of metronidazole, neomycin, ampicillin (1 g/l each) and vancomycin (0.5 g/l) for one week to partially eliminate intestinal microbiota. Arthritis was assessed macroscopically and by histologic analysis. Differentiation of Th1, Th17 and regulatory T (Treg) cells and production of their prototypic cytokines in intestinal lamina propria and joint-draining lymph nodes were assessed by flow cytometry and Luminex array. Development of anti-collagen type II antibodies was assessed in serum of CIA mice using ELISA. Intestinal and synovial expression of cytokines and serum amyloid A (SAA) isotypes was measured by qPCR.

Results: Elimination of intestinal microbiota in mice with ongoing CIA specifically suppressed intestinal Th17 cell differentiation without affecting Th1 and Treg cells. Accordingly, production of interleukin-17 (IL-17), but not interferon γ, IL-4 and IL-10, by lamina propria lymphocytes was significantly diminished in antibiotic-treated mice. Furthermore, intestinal expression of SAA isoforms and IL-22, known to promote lamina propria Th17 cell differentiation, was suppressed in antibiotic-treated CIA mice. Importantly, elimination of intestinal microbiota resulted in suppressed Th17 cell differentiation and IL-17 production in joint-draining lymph nodes and reduced the severity of established CIA. In contrast, antibiotic treatment did not influence disease severity in the T cell-independent K/BxN serum-transfer arthritis. Intriguingly, the abundance of intestinal Th17 cells strongly correlated with the severity of arthritis in the CIA mice. However, elimination of intestinal microbiota after disease onset did not affect the development of anti-collagen type II autoantibodies.  

Conclusion : These observations suggest that modulation of commensal intestinal microbiota during established arthritis specifically suppress Th17 differentiation and dampen T cell-mediated arthritic processes. While our study does not advocate the use of antibiotics as a treatment for RA, it supports the notion that inflammatory signals provided by the gut microbiota continue to promote arthritis after its onset. Understanding the exact mechanisms linking the intestinal T cell response with arthritis may help identifying novel therapeutic strategies for RA.


Disclosure: R. Rogier, None; H. Evans-Marin, None; B. Walgreen, None; M. M. Helsen, None; L. van den Bersselaar, None; P. M. van der Kraan, None; F. A. J. van de Loo, None; P. L. van Lent, None; J. U. Scher, None; W. B. van den Berg, None; M. I. Koenders, None; S. Abdolahi-Roodsaz, None.

To cite this abstract in AMA style:

Rogier R, Evans-Marin H, Walgreen B, Helsen MM, van den Bersselaar L, van der Kraan PM, van de Loo FAJ, van Lent PL, Scher JU, van den Berg WB, Koenders MI, Abdolahi-Roodsaz S. Partial Elimination of Intestinal Microbiota Dampens T Helper 17 Cell Differentiation and Established Collagen-Induced Arthritis in Mice [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/partial-elimination-of-intestinal-microbiota-dampens-t-helper-17-cell-differentiation-and-established-collagen-induced-arthritis-in-mice/. Accessed January 15, 2021.
  • Tweet
  • Email
  • Print
Save to PDF

« Back to 2016 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/partial-elimination-of-intestinal-microbiota-dampens-t-helper-17-cell-differentiation-and-established-collagen-induced-arthritis-in-mice/

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.