Systemic Sclerosis Dermal Fibroblasts Suppress Th1 Cytokine Production via Galectin-9 Overproduction due to Fli1 Deficiency

The Journal of Investigative Dermatology
Ryosuke SaigusaShinichi Sato

Abstract

Dermal fibroblasts promote skin-localized transdifferentiation of regulatory T cells to T helper (Th) type 2-like cells in systemic sclerosis (SSc). However, the entire effect of SSc dermal fibroblasts on immune cells still remains unknown. Because galectin-9 induces Th2 cytokine-predominant immune imbalance by negatively regulating Th1/Th17 cells in inflammatory diseases, we investigated the contribution of galectin-9 to Th immune balance in SSc lesional skin. We used human clinical samples and Fli1+/- mice because Fli1 deficiency induces SSc-like phenotypes in various cell types. Galectin-9 was overexpressed in SSc dermal fibroblasts in vivo and in vitro. Serum galectin-9 levels were significantly elevated in SSc patients and positively correlated with skin score. Galectin-9 was up-regulated by autocrine endothelin stimulation and Fli1 deficiency, and Fli1 occupied the LGALS9 promoter in dermal fibroblasts. Co-culture of splenic CD4+ T cells with Fli1+/- dermal fibroblasts significantly increased IL-4-producing cell proportion, and this effect was cancelled in parallel with the increased interferon-γ production when Fli1+/- dermal fibroblasts were transfected with Lgals9 small interfering RNA. Furthermore, Lgals9 small interf...Continue Reading

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Citations

Sep 21, 2018·Current Opinion in Rheumatology·Patrizia Fuschiotti
Dec 7, 2018·Journal of the European Academy of Dermatology and Venereology : JEADV·T MiyagawaS Sato
Dec 12, 2017·The Journal of Dermatology·Yoshihide Asano
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May 11, 2021·Autoimmunity Reviews·Wang-Dong XuAn-Fang Huang
Jul 7, 2021·Drug Discovery Today·Leyla Norouzi-Barough, Ardeshir Bayat

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