Controlling autoimmune diabetes onset by targeting Protease-Activated Receptor 2

Gal Reches, Lynn Khoon, Narmeen Ghanayiem, Assaf Malka, Ron Piran

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Type 1 diabetes (T1D) is a challenging autoimmune disease, characterized by an immune system assault on insulin-producing β-cells. As insulin facilitates glucose absorption into cells and tissues, β-cell deficiency leads to elevated blood glucose levels on one hand and target-tissues starvation on the other. Despite efforts to halt β-cell destruction and stimulate recovery, success has been limited. Our recent investigations identified Protease-Activated Receptor 2 (Par2) as a promising target in the battle against autoimmunity. We discovered that Par2 activation's effects depend on its initial activation site: exacerbating the disease within the immune system but fostering regeneration in affected tissue. Methods: We utilized tissue-specific Par2 knockout mice strains with targeted Par2 mutations in β-cells, lymphocytes, and the eye retina (as a control) in the NOD autoimmune diabetes model, examining T1D onset and β-cell survival. Results: We discovered that Par2 expression within the immune system accelerates autoimmune processes, while its presence in β-cells offers protection against β-cell destruction and T1D onset. This suggests a dual-strategy treatment for T1D: inhibiting Par2 in the immune system while activating it in β-cells, offering a promising strategy for T1D. Conclusions: This study highlights Par2's potential as a drug target for autoimmune diseases, particularly T1D. Our results pave the way for precision medicine approaches in treating autoimmune conditions through targeted Par2 modulation.

Original languageEnglish
Article number116622
JournalBiomedicine and Pharmacotherapy
Volume175
DOIs
StatePublished - Jun 2024

Bibliographical note

Publisher Copyright:
© 2024

Keywords

  • Autoimmunity
  • Pancreatic β-cells
  • Protease Activated Receptor 2 (Par2)
  • Tissue-specific mutation
  • Type 1 diabetes

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