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Related Concept Videos

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Related Experiment Video

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Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity
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Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis.

David A McBride1,2, Matthew D Kerr1,2, Wade T Johnson1

  • 1Department of Nanoengineering, University of California, La Jolla, San Diego, CA, 92093, USA.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 9, 2023
PubMed
Summary

This study introduces a novel immunoregulatory approach using sustained release of all-trans retinoic acid (ATRA) via microparticles for treating autoimmune arthritis. This method enhances regulatory T cells, reducing joint inflammation and damage without generalized immune suppression.

Keywords:
immune engineeringregulatory T cellsrheumatoid arthritis

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Area of Science:

  • Immunology
  • Rheumatology
  • Drug Delivery Systems

Background:

  • Conventional disease-modifying antirheumatic drugs (DMARDs) show limited efficacy in a significant portion of patients with autoimmune inflammatory arthritides.
  • There is a need for novel therapeutic strategies that can effectively manage autoimmune arthritis while minimizing systemic side effects.

Purpose of the Study:

  • To investigate the potential of sustained, joint-localized release of all-trans retinoic acid (ATRA) using biodegradable microparticles as a disease-modifying treatment for autoimmune arthritis.
  • To elucidate the immunoregulatory mechanisms underlying ATRA's therapeutic effects in the context of arthritis.

Main Methods:

  • Development and intra-articular (IA) injection of poly-(lactic-co-glycolic) acid (PLGA)-based biodegradable microparticles encapsulating ATRA (PLGA-ATRA MP) in mouse models of autoimmune arthritis.
  • Assessment of T cell differentiation, regulatory T cell (Treg) populations, joint inflammation, and structural damage (proteoglycan loss, bone erosions).
  • Evaluation of systemic immune effects and disease modification in both injected and uninjected joints.

Main Results:

  • IA PLGA-ATRA MP administration led to sustained joint-localized ATRA release, enhancing anti-inflammatory regulatory T cells (Tregs).
  • This approach effectively reduced joint inflammation, proteoglycan loss, and bone erosions in SKG and collagen-induced arthritis mouse models.
  • Therapeutic effects were observed in both injected and uninjected joints, mimicking the effects of IA Treg injection, without causing generalized immune suppression.

Conclusions:

  • Sustained intra-articular delivery of ATRA via PLGA microparticles represents a promising immunoregulatory strategy for autoimmune arthritis.
  • This localized approach modulates immune responses to protect joints and control systemic disease, offering a potential alternative to conventional DMARDs.
  • PLGA-ATRA MP demonstrate potential for development as a targeted disease-modifying agent for autoimmune arthritis.