%0 Journal Article
%T VISTA Deficiency Exacerbates the Development of Pulmonary Fibrosis by Promoting Th17 Differentiation.
%A Xie H
%A Zhong X
%A Chen J
%A Wang S
%A Huang Y
%A Yang N
%J J Inflamm Res
%V 17
%N 0
%D 2024
%M 38911987
%F 4.631
%R 10.2147/JIR.S458651
%X UNASSIGNED: Interstitial lung disease (ILD), characterized by pulmonary fibrosis (PF), represents the end-stage of various ILDs. The immune system plays an important role in the pathogenesis of PF. V-domain immunoglobulin suppressor of T-cell activation (VISTA) is an immune checkpoint with immune suppressive functions. However, its specific role in the development of PF and the underlying mechanisms remain to be elucidated.
UNASSIGNED: We assessed the expression of VISTA in CD4 T cells from patients with connective tissue disease-related interstitial lung disease (CTD-ILD). Spleen cells from wild-type (WT) or Vsir -/- mice were isolated and induced for cell differentiation in vitro. Additionally, primary lung fibroblasts were isolated and treated with interleukin-17A (IL-17A). Mice were challenged with bleomycin (BLM) following VISTA blockade or Vsir knockout. Moreover, WT or Vsir -/- CD4 T cells were transferred into Rag1 -/- mice, which were then challenged with BLM.
UNASSIGNED: VISTA expression was decreased in CD4 T cells from patients with CTD-ILD. Vsir deficiency augmented T-helper 17 (Th17) cell differentiation in vitro. Furthermore, IL-17A enhanced the production of inflammatory cytokines, as well as the differentiation and migration of lung fibroblasts. Both VISTA blockade and knockout of Vsir increased the percentage of IL-17A-producing Th17 cells and promoted BLM-induced PF. In addition, mice receiving Vsir -/- CD4 T cells exhibited a higher percentage of Th17 cells and more severe PF compared to those receiving WT CD4 T cells.
UNASSIGNED: These findings demonstrate the significant role of VISTA in modulating the development of PF by controlling Th17 cell differentiation. These insights suggest that targeting VISTA could be a promising therapeutic strategy for PF.