Systemic sclerosis (SSc) is an idiopathic systemic connective tissue disorder characterized by fibrosis of the skin and internal organs, with growing interest in the imbalance between Th17 cells and regulatory T cells (Tregs) in the disease's pathogenesis. Heligmosomoides polygyrus (Hp), a natural intestinal parasite of mice, is known to induce Tregs in the host. We aimed to investigate the effects of Hp-induced Tregs on bleomycin-induced dermal fibrosis and clarify the role of the Th17/Treg balance in SSc fibrosis. Infection with Hp suppressed the development of bleomycin-induced dermal fibrosis and the infiltration of CD3+ T cells and CD68+ macrophages. Flow cytometric analysis revealed that Hp infection increased Tregs and inhibited the induction of bleomycin-induced Th17 cells. Treg depletion nullified these effects, suggesting that Hp-induced Tregs may prevent bleomycin-induced dermal fibrosis and inflammation. Analysis of the intestinal microbiota showed that bacteria positively correlated with Tregs exhibited a negative correlation with Th17 cells and dermal fibrosis in mice. SSc patients with severe fibrosis displayed a distinct microbiota profile. These results suggest that alterations in the intestinal microbiota may contribute to the Th17/Treg imbalance in SSc and its progression. Enhancing Tregs to regulate the Th17/Treg imbalance may present a promising strategy for suppressing fibrosis in SSc.
Keywords: Heligmosomoides polygilus; Bleomycin; Fibrosis; Microbiota; Systemic sclerosis; Th17/Treg balance.
© 2025. The Author(s).