Transforming growth factor beta (TGF-β) induces type 1 interferon signalling in systemic sclerosis keratinocytes through the chloride intracellular channel 4 (CLIC4).

ABSTRACT:

Objectives

Systemic sclerosis (SSc) is an autoimmune disease, which is characterized by fibrosis of the skin, progressing to affect the internal organs in the most serve cases. Type 1 interferon (IFN) signalling plays a major role in SSc disease progression. The cytokine TGF-β has been extensively shown to be a major driver of fibrosis but its role in the induction of the type 1 interferon response is poorly understood.

Methods

Type 1 IFN signalling was activated in keratinocytes using a range of agonists, IFN2α, Poly I:C, Poly dA:dT, LPS and TGF-β. CLIC4 activity was inhibited with the small molecule chloride channel inhibitors NPPB, IAA:94 and siRNA specific to CLIC4. Conditioned media collected from Healthy and SSc dermal fibroblasts was used to stimulate keratinocytes.

SUBMITTER: Wasson CW 

PROVIDER: S-EPMC12400655 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature