Restoration of Fli1 expression as a potential therapeutic approach in Systemic Sclerosis: Effects on age-associated B cells

Abstract

Fli1 is a transcription factor playing a major role in the regulation of normal hematopoiesis and vasculogenesis. Its deficiency has been associated with the development of fibrosis in various diseases, including systemic sclerosis/scleroderma (SSc), a rare autoimmune rheumatic disease. In addition, in Fli1 B cell conditional knockout mice, a striking increase of age-associated B cells (ABCs) has been observed. These cells constitute a CD11c⁺CD21^low/- B cell population that displays an expansion in autoimmunity and drives disease pathogenesis. The exact role and functions of ABCs, though, are not yet fully understood. Taking into consideration all the above, regarding Fli1 deficiency in SSc pathogenesis and ABC expansion, we propose restoration of this specific transcription factor’s expression as a potential therapeutic approach for the aforementioned rheumatic disease. Moreover, we provide some interventions that aim to restore Fli1 expression via modulating the signals of TGF-β pathway, whose activation is considered as crucial for fibrosis development in SSc.