Treg Depletion Attenuated Silica-Induced Lung Fibrosis

A recent study published in PlosOne by Dr. Chen and associates suggested that depletion of Tregs with anti-CD25 mAb attenuated silica-induced lung fibrosis. Depletion of CD4+CD25+Foxp3+ Treg cells enhanced Th1 response and decelerated Th1/Th2 balance toward a Th2 phenotype in silica-induced lung fibrosis. These suggested that Treg cells regulated the inflammation against silica via suppression of inflammatory cells in the early stage and Treg cells may modulate Th1/Th2 polarization toward a Th2 dominant response by suppressing Th1 response in experimental model of silica-induced lung fibrosis.

Unfortunately, the study did not show collagen changes.

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015404

CD4+CD25+Foxp3+ Regulatory T Cells Depletion May Attenuate the Development of Silica-Induced Lung Fibrosis in Mice

Fangwei Liu, Jie Liu, Dong Weng, Ying Chen, Laiyu Song, Qincheng He, Jie Chen*

Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, People's Republic of China

Abstract
Background

Silicosis is an occupational lung disease caused by inhalation of silica dust characterized by lung inflammation and fibrosis. Previous study showed that Th1 and Th2 cytokines are involved in silicosis, but Th1/Th2 polarization during the development of silicosis is still a matter of debate. Regulatory T cells (Treg cells) represent a crucial role in modulation of immune homeostasis by regulating Th1/Th2 polarization, but their possible implication in silicosis remains to be explored.
Methodology/Principal Findings

To evaluate the implication of Treg cells in the development of silicosis, we generated the Treg-depleted mice model by administration of anti-CD25 mAbs and mice were exposed to silica by intratracheal instillation to establish experimental model of silica-induced lung fibrosis. The pathologic examinations show that the Treg-depleted mice are susceptive to severer inflammation in the early stage, with enhanced infiltration of inflammatory cells. Also, depletion of Treg cells causes a delay of the progress of silica-induced lung fibrosis in mice model. Further study of mRNA expression of cytokines reveals that depletion of Tregs leads to the increased production of Th1-cytokines and decreased production of Th2-cytokine. The Flow Cytometry and realtime PCR study show that Treg cells exert the modulation function both directly by expressing CTLA-4 at the inflammatory stage, and indirectly by secreting increasing amount of IL-10 and TGF-β during the fibrotic stage in silica-induced lung fibrosis.
Conclusion/Significance

Our study suggests that depletion of Tregs may attenuate the progress of silica-induced lung fibrosis and enhance Th1 response and decelerate Th1/Th2 balance toward a Th2 phenotype in silica-induced lung fibrosis. The regulatory function of Treg cells may depend on direct mechanism and indirect mechanism during the inflammatory stage of silicosis.