Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice.

ABSTRACT:

Background

Tyrosine protein-kinase 2 (TYK2) mediates inflammatory signalling through multiple cytokines, including interferon-α (IFNα), interleukin (IL)-12, and IL-23. TYK2 missense mutations protect against type 1 diabetes (T1D), and inhibition of TYK2 shows promise in other autoimmune conditions.

Methods

We evaluated the effects of specific TYK2 inhibitors (TYK2is) in pre-clinical models of T1D, including human β cells, cadaveric islets, iPSC-derived islets, and mouse models.

Findings

In vitro studies showed that TYK2is prevented IFNα-induced β cell HLA class I up-regulation, endoplasmic reticulum stress, and chemokine production. In co-culture studies, pre-treatment of β cells with TYK2i prevented IFNα-induced antigenic peptide presentation and alloreactive and aut

SUBMITTER: Syed F 

PROVIDER: S-EPMC12173048 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature