Regulatory Effect of PD1/PD-Ligand 1 (PD-L1) on Treg Cells in Patients with Idiopathic Pulmonary Fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a serious irreversible lung disease. The mechanism of immune checkpoint in idiopathic pulmonary fibrosis is still unknown.
MATERIAL AND METHODS: First, the expression levels of PD-1/PD-L1 on the surface of CD4+ T cells and the proportion of Treg cells in IPF or controls were detected by flow cytometry. Then, expression of TGF-ß in blood samples was detected with ELISA. Moreover, a co-culture system was composed of fibroblasts stimulated by TGF-ß and CD4+ T cells from healthy people. The proportions of Treg cells and PD-1 in the co-culture system were detected. In addition, we detected the proportion of Treg cells and the level of collagen-1 after adding PD-1 or PD-L1 protein antibody blocker to the co-culture system.
RESULTS: Flow cytometry revealed the upregulated expression of PD-1/PD-L1 in CD4+ T cells of IPF patients. PD-1 appears to inhibit the differentiation of CD4+ T cells into Treg cells. Co-culture of myofibroblasts and CD4+ T cells induced the generation of collagen-1 and reduced the proliferation of CD4+ T cells. When PD-1 was blocked, the inhibition of Treg cell differentiation was reversed, accompanied by decreased collagen-1 production.
CONCLUSIONS: This work identified the molecular mechanism of PD-1 in patients with IPF. It may provide a new perspective on the therapeutic effect of PD-1.

Keywords: idiopathic pulmonary fibrosis, Programmed Cell Death 1 Receptor, T-Lymphocytes, T-Lymphocytes, Regulatory