Details

Autor(en) / Beteiligte

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

Titel

Controlling autoimmune diabetes onset by targeting Protease-Activated Receptor 2

Ist Teil von

• Biomedicine & pharmacotherapy, 2024-06, Vol.175, p.116622, Article 116622

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2024

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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. [Display omitted] •Par2 identified as key in Type 1 diabetes, with contradicting roles.•Par2 knockout mice were used to solve Par2 functions on Type 1 diabetes.•Par2 dual modulation strategy suggested for Type 1 diabetes treatment.•Highlights Par2 as a promising therapeutic target in Type 1 diabetes.•Advances precision medicine for autoimmune diseases via Par2 dual modulation.