Deleterious Role of Th9 Cells in Pulmonary Fibrosis.

Kui Miao Deng,Xiao Xiao Tang,Xiang Sheng Yang,Qing Yang Yu,Yi Xin She,Qun Luo

doi:10.3390/cells10113209

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease of unknown etiology. Immune disorders play an important role in IPF pathogenesis. Here, we show that Th9 cells differentiate and activate in the lung tissue of patients with IPF and bleomycin (BLM)-induced lung fibrosis mice. Moreover, we found that Th9 cells promote pulmonary fibrosis in two ways. On the one hand, Th9 cells promote fibroblast differentiation, activation, and collagen secretion by secreting IL-9. On the other hand, they promote differentiation of Th0 cells into Th2 cells by secreting IL-4. Th9 cells and Th2 cells can promote each other, accelerating the Th1/Th2 imbalance and eventually forming a positive feedback of pulmonary fibrosis. In addition, we found that neutralizing IL-9 in both preventive and therapeutic settings ameliorates bleomycin-induced pulmonary fibrosis. Furthermore, we identified several critical signaling pathways involved in the effect of neutralizing IL-9 on pulmonary fibrosis by proteomics study. From an immunological perspective, we elucidated the novel role and underlying mechanism of Th9 cells in pulmonary fibrosis. Our study suggested that Th9-based immunotherapy may be employed as a treatment strategy for IPF.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, incurable, and fatal disease characterized by pulmonary fibrosis [1]
Previous studies have shown that TGF-β and IL-4 are elevated in patients with IPF (TGF-β is increased in lung tissue and IL-4 is increased in bronchoalveolar lavage fluid (BALF))
The results showed that the proportion of Th9 cells in CD4+ T lymphocytes in the peripheral blood mononuclear cells (PBMC) of patients with IPF was significantly higher than that in healthy controls (Figure 1B) and positively correlated with CT score (Figure 1C), indicating that the increase of Th9 cells is positively correlated with the severity of pulmonary fibrosis in patients with IPF

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, incurable, and fatal disease characterized by pulmonary fibrosis [1]. The incidence of IPF has continued to increase in recent years and the disease course is irreversible. The pathogenesis of IPF is not completely understood, and currently there is no effective treatment. The two oral drugs approved by the US FDA, nintedanib and pirfenidone, can only relieve symptoms or slow disease progression. The latest guidelines just weakly recommended them for IPF drug treatment [1]. Several drugs have been tested in clinical trials, but their effects are limited [4]. Development of new and effective treatment strategies has been of great significance and is desperately needed

Methods

Results

Conclusion