The Rheumatologist
COVID-19 News
  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed
  • Home
  • Conditions
    • Rheumatoid Arthritis
    • SLE (Lupus)
    • Crystal Arthritis
      • Gout Resource Center
    • Spondyloarthritis
    • Osteoarthritis
    • Soft Tissue Pain
    • Scleroderma
    • Vasculitis
    • Systemic Inflammatory Syndromes
    • Guidelines
  • Resource Centers
    • Axial Spondyloarthritis Resource Center
    • Gout Resource Center
    • Psoriatic Arthritis Resource Center
    • Rheumatoid Arthritis Resource Center
    • Systemic Lupus Erythematosus Resource Center
  • Drug Updates
    • Biologics & Biosimilars
    • DMARDs & Immunosuppressives
    • Topical Drugs
    • Analgesics
    • Safety
    • Pharma Co. News
  • Professional Topics
    • Ethics
    • Legal
    • Legislation & Advocacy
    • Career Development
      • Certification
      • Education & Training
    • Awards
    • Profiles
    • President’s Perspective
    • Rheuminations
    • Interprofessional Perspective
  • Practice Management
    • Billing/Coding
    • Quality Assurance/Improvement
    • Workforce
    • Facility
    • Patient Perspective
    • Electronic Health Records
    • Apps
    • Information Technology
    • From the College
    • Multimedia
      • Audio
      • Video
  • Resources
    • Issue Archives
    • ACR Convergence
      • Systemic Lupus Erythematosus Resource Center
      • Rheumatoid Arthritis Resource Center
      • Gout Resource Center
      • Abstracts
      • Meeting Reports
      • ACR Convergence Home
    • American College of Rheumatology
    • ACR ExamRheum
    • Research Reviews
    • ACR Journals
      • Arthritis & Rheumatology
      • Arthritis Care & Research
      • ACR Open Rheumatology
    • Rheumatology Image Library
    • Treatment Guidelines
    • Rheumatology Research Foundation
    • Events
  • About Us
    • Mission/Vision
    • Meet the Authors
    • Meet the Editors
    • Contribute to The Rheumatologist
    • Subscription
    • Contact
  • Advertise
  • Search
You are here: Home / Articles / Local Depletion of Resident Memory T Cells May Reduce Site-Specific Joint Flares

Local Depletion of Resident Memory T Cells May Reduce Site-Specific Joint Flares

April 21, 2020 • By Carina Stanton

  • Tweet
  • Email
Print-Friendly Version / Save PDF

ATLANTA—People with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) have recurring joint inflammation with a strong tendency to flare. Past research led by Margaret Chang, MD, PhD, a pediatric rheumatologist in the Division of Immunology at Boston Children’s Hospital, used a novel murine model to identify a population of memory T cells that persist in the synovium with a distinct resident memory T cell phenotype in recurrent, joint-specific inflammation.1

You Might Also Like
  • Atmospheric & Environmental Changes Tied to Organ-Specific Lupus Flares
  • Naive B Cells Activate & Expand During Lupus Flares
  • Plasma Cells, Synovial Compartment Implicated in Tenacity of Rheumatoid Arthritis
Also By This Author
  • More Money, More Research: Foundation Report Sheds Light on Funding Gaps

Last fall at the 2019 ACR/ARP Annual Meeting, Dr. Chang and her colleagues presented their latest findings on these cells as a potential target to reduce arthritic flare.2

ad goes here:advert-1
ADVERTISEMENT
SCROLL TO CONTINUE

Targeting Flares
Resident memory T cells are site-specific memory T cells that reside long term in peripheral tissues as a defense against pathogens. However, these cells can also cause recurrent inflammation locally. Certain rheumatologic diseases, such as RA and JIA, are characterized by recurrent joint inflammation that exhibits a strong tendency to flare at the same sites.

To understand how resident memory T cells may be manipulated for therapeutic aims, Dr. Chang and colleagues used a murine model of site-specific recurrent synovitis.1 They used intra-articular injection of adeno-associated virus to label synovial T cells in fluorescent reporter mice, tracking the site-specific persistence of resident memory T cells. They used a single intra-articular injection of diphtheria toxin in mice with Lck-inducible diphtheria toxin receptors to locally deplete synovial T cells prior to triggering an arthritis flare. Depletion of synovial T-cells made the joint relatively resistant to developing inflammatory arthritis. This approach demonstrated the contribution of synovial resident memory T cells to the flare response.

ad goes here:advert-2
ADVERTISEMENT
SCROLL TO CONTINUE

The results showed synovial resident memory T cells persist in previously inflamed joints eight months after remission and retain their capacity to trigger site-specific flare. Adeno-associated, virus-labeled resident memory T cells present in the synovium during remission did not migrate to the contralateral joint. These cells enabled joint inflammation by recruiting effector lymphocytes to the joint, and correspondingly, the localized depletion of resident memory T cells strongly blunted the capacity to trigger flare arthritis.

Managing Flares Without Immunosuppression
Dr. Chang says the hope is to target resident memory T cells in the joints experiencing flares and deplete the cells locally.

“Many of our patients with RA and JIA have to remain on systemic therapies to stay in remission. By locally depleting these [resident memory T cells], we theorize that sustained disease control or even an effective cure could be achieved without the need for systemic immunosuppression,” she says.

ad goes here:advert-3
ADVERTISEMENT
SCROLL TO CONTINUE

“As a pediatric rheumatologist, JIA patients are foremost in my mind,” Dr. Chang says. “Local [resident memory T cell] depletion would be an ideal strategy for patients with RA or JIA who are in remission, but are unable to come off of systemic immunosuppressive medications.”

Currently, Dr. Chang and colleagues are working on multiple fronts to further investigate resident memory T cells activity and arthritis flares. They are trying to understand how these cells are formed in the joint and how they interact with other cells in the synovium to trigger a flare. 

“Most importantly, we are working on developing a more effective way of targeting these cells and how to translate this [approach] into a system that can be used in patients,” Dr. Chang says.


Carina Stanton is a freelance science journalist based in Denver.

References

  1. Chang MH, Levescot A, Morris A, et al. Murine model of arthritis flare identifies CD8+ tissue resident memory T cells in recurrent synovitis [abstract]. Arthritis Rheumatol. 2017 Oct;69(suppl 4).
  2. Chang M, Levescot A, Blaustein R, et al. Persistent synovial resident memory T cells mediate arthritis flares [abstract]. Arthritis Rheumatol. 2019 Oct;71(suppl 10).

Pages: 1 2 | Multi-Page

Filed Under: Conditions, Rheumatoid Arthritis Tagged With: 2019 ACR/ARP Annual Meeting, Flares, joint, juvenile idiopathic arthritis (JIA), Rheumatoid Arthritis (RA)

You Might Also Like:
  • Atmospheric & Environmental Changes Tied to Organ-Specific Lupus Flares
  • Naive B Cells Activate & Expand During Lupus Flares
  • Plasma Cells, Synovial Compartment Implicated in Tenacity of Rheumatoid Arthritis
  • Peripheral Helper Cells May Provide Clue to RA Pathology

ACR Convergence

Don’t miss rheumatology’s premier scientific meeting for anyone involved in research or the delivery of rheumatologic care or services.

Visit the ACR Convergence site »

Rheumatology Research Foundation

The Foundation is the largest private funding source for rheumatology research and training in the U.S.

Learn more »

American College of Rheumatology

Visit the official website for the American College of Rheumatology.

Visit the ACR »

The Rheumatologist newsmagazine reports on issues and trends in the management and treatment of rheumatic diseases. The Rheumatologist reaches 11,500 rheumatologists, internists, orthopedic surgeons, nurse practitioners, physician assistants, nurses, and other healthcare professionals who practice, research, or teach in the field of rheumatology.

About Us / Contact Us / Advertise / Privacy Policy / Terms of Use

  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed

Copyright © 2006–2022 American College of Rheumatology. All rights reserved.

ISSN 1931-3268 (print)
ISSN 1931-3209 (online)