Transdermal Microneedles Alleviated Rheumatoid Arthritis by Inducing Immune Tolerance via Skin-Resident Antigen Presenting Cells

Yuanhao Zhao, Xiaoyan Chen, Penghui He, Xuanyu Wang, Yanhua Xu, Rui Hu, Yangsen Ou, Zhihua Zhang, Zhibing Zhang, Guangsheng Du*, Xun Sun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Restoring immune tolerance is the ultimate goal for rheumatoid arthritis (RA) treatment. The most reported oral or intravenous injection routes for the immunization of autoantigens cause gastrointestinal side effects, low patient compliance, and unsatisfied immune tolerance induction. Herein, the use of a transdermal microneedle patch is for the first time investigated to codeliver CII peptide autoantigen and rapamycin for reversing immune disorders of RA. The immunized microneedles efficiently recruit antigen-presenting cells particularly Langerhans cells, and induce tolerogenic dendritic cells at the administration skin site. The tolerogenic dendritic cells further homing to lymph nodes to activate systemic Treg cell differentiation, which upregulates the expression of anti-inflammatory mediators while inhibiting the polarization of Th1/2 and Th17 T cell phenotypes and the expression of inflammatory profiles. As a result, the optimized microneedles nearly completely eliminate RA symptoms and inflammatory infiltrations. Furthermore, it is demonstrated that a low dose of rapamycin is crucial for the successful induction of immune tolerance. The results indicate that a rationally designed microneedle patch is a promising strategy for immune balance restoration with increased immune tolerance induction efficiency and patient compliance.

Original languageEnglish
Article number2307366
JournalSmall
Early online date1 Dec 2023
DOIs
Publication statusE-pub ahead of print - 1 Dec 2023

Bibliographical note

Funding Information:
The authors thank the support of the research by the Natural Science Foundation of China (Grant Nos. 82003684 & 81925036 & 82341038), Natural Science Foundation of Sichuan Province (2022NSFSC1491), China Postdoctoral Science Foundation Grant (2019M663534), Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System (CARS‐SVDIP), the Fundamental Research Funds for the Central Universities and Sichuan University Postdoctoral Interdisciplinary Innovation Fund.

Publisher Copyright:
© 2023 Wiley-VCH GmbH.

Keywords

  • CII peptide
  • immune tolerance
  • rapamycin
  • rheumatoid arthritis
  • transdermal microneedle patch

ASJC Scopus subject areas

  • Biotechnology
  • General Chemistry
  • Biomaterials
  • General Materials Science
  • Engineering (miscellaneous)

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