CD4+CD25+ Tregs as dependent factor in the course of bleomycin-induced pulmonary fibrosis in mice

Abstract

The immune system is felt to play an essential role in pulmonary fibrosis (PF). CD4⁺CD25⁺ regulatory T cells (Tregs) are crucial in maintaining immune tolerance and immune homeostasis, but their role in the pathogenesis of PF is controversial and still unclear. We here explored the relationship between peripheral blood CD4⁺CD25⁺ Tregs and the course of bleomycin-induced PF in mice. Mouse PF models were established by intratracheal instillation of bleomycin. Lung histology, hydroxyproline, Th1/Th2 balanc, CD4⁺CD25⁺ Tregse were analyzed at the 3rd，7th，14th，21st and 28th days after instillation. CD4⁺CD25⁺ Tregs were also transferred into mice with or without PF by tail vein injection. The trend of CD4⁺CD25⁺ Tregs changes was increased firstly, decreased, increased again from 7th to 28th days after bleomycin instillation, which had great relevance with alveolitis and fibrosis scores. There also were high Th1 polarization index from 3rd to 14th days and high Th2 polarization index at 21st and 28th days after bleomycin treatment. CD4⁺CD25⁺ Tregs could promote the secretion of Th2 cytokines and inhibit the secretion of Th1 cytokines, allow the Th1/Th2 balance to Th2 direction in PF. Moreover, preventive adoptive transfer of CD4⁺CD25⁺ Tregs may ameliorate the process of PF, while acute adoptive transfer of CD4⁺CD25⁺ Tregs may aggravate the process of PF. These findings suggested that the dynamic changes of CD4⁺CD25⁺ Tregs as dependent factor might designate a different course of PF induced by bleomycin in mice, and might be a selected drug use indicator for therapy of PF.

Keywords: Bleomycin; CD4(+)CD25(+) regulatory T cells; Pulmonary fibrosis; Th1/Th2 balance.