STING-STAT6 Signaling Pathway Promotes IL-4⁺ and IFN-α⁺ Fibrotic T Cell Activation and Exacerbates Scleroderma in SKG Mice.

ABSTRACT: Systemic sclerosis (SS) is an autoimmune disease and pathological mechanisms of SS are unclear. In this study, we investigated the role of T cells in the progression of SS using SKG mice and humanized mice. SKG mice have a spontaneous point mutation in ZAP70. We induced scleroderma in SKG mice and a humanized SS mouse model to assess whether T cell-mediated immune responses induce SS. As a result, we found increased dermal thickness, fibrosis, and lymphocyte infiltration in skin tissue in SKG SS mice compared to BALB/c mice (control). Also, blood cytokine level, including IL-4- and IFN-α which are produced by CD4⁺ T cells via STIM1/STING/STAT6/IRF3 signaling pathways, were increased in SKG mice. Interestingly, skin fibrosis was reduced by inhibiting STING pathway in skin fibrobl

SUBMITTER: Lee KH 

PROVIDER: S-EPMC11538607 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature