Abstract
BackgroundHigh expression of chemokine (C-X3-C motif) receptor 1 (CX3CR1) was shown to contribute to the progression of many fibrotic diseases. However, there is still no study for the role of CX3CR1 in idiopathic pulmonary fibrosis (IPF). Therefore, we aimed to identify CX3CR1-related immune infiltration genes (IIGs) in IPF and establish a combined risk model to evaluate the prognosis of IPF.MethodsA discovery cohort of IPF patients (GSE70867) was downloaded from the Gene Expression Omnibus dataset. We identified the composition of 22 kinds of immune cells infiltration by CIBERSORT. The Cox regression model with the LASSO method was used for identifying prognostic genes and developing CX3CR1-related IIGs. Kaplan–Meier was applied to plot the survival curve of prognosis model. Peripheral blood mononuclear cell (PBMC) and bronchoalveolar lavage fluid (BALF) were collected to be tested by quantitative reverse transcriptase-PCR (qRT-PCR) from 15 clinical samples, including 8 healthy controls (HC), 4 patients with usual interstitial pneumonia (UIP) and 3 patients with pulmonary fibrosis (FIB).ResultsWe found that high expression of CX3CR1 in BALF contributed to the poor prognosis in IPF patients. ALR4C, RAB37, GPR56, MARCKS, PXN and RASSF2 were identified as CX3CR1-related IIGs, which were highly expressed in PBMC of UIP/FIB patients than that of HC. Moreover, the expression of PXN was higher in FIB patients’ PBMC than that of UIP ones. In the cohort of IPF patients, high infiltration of activated NK cells in BALF caused poor survival compared to low infiltration group. The infiltration of activated NK was regulated by CX3CR1-related IIGs. The combined risk model predicted that high expression of CX3CR1-related IIGs and high infiltrated activated NK cells caused poor prognosis in IPF patients.ConclusionWe identified a group of CX3CR1-related IIGs in IPF patients. This combined risk model provided new insights in the prognosis and therapy of IPF.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a consequence of recurrent microinjuries to alveolar epithelium cells, triggering an abnormal fibrotic response in the lung parenchyma of a genetically susceptible individual [1]
We found that high expression of CX3CR1 in bronchoalveolar lavage fluid (BALF) contributed to the poor prognosis in IPF patients
ALR4C, RAB37, G protein-coupled receptor 56 (GPR56), Myristoylated alanine-rich C-kinase substrate (MARCKS), PXN and RASSF2 were identified as CX3CR1-related infiltration genes (IIGs), which were highly expressed in Peripheral blood mononuclear cell (PBMC) of usual interstitial pneumonia (UIP)/FIB patients than that of healthy controls (HC)
Summary
Idiopathic pulmonary fibrosis (IPF) is a consequence of recurrent microinjuries to alveolar epithelium cells, triggering an abnormal fibrotic response in the lung parenchyma of a genetically susceptible individual [1]. Chemokine (C-X3-C motif) Receptor 1 (CX3CR1) is mainly expressed on most of myeloid cells [3] and combined with its only ligand CX3CL1 to mediate chemotaxis and adhesion of immune cells [4]. The role of CX3CR1 in the progression of organ fibrosis is still controversial. Several studies showed that high expression of CX3CR1 resulted in the exacerbation of obstruction-induced renal fibrosis and bleomycin-induced pulmonary fibrosis [3, 5]. There were some studies which demonstrated that high expression of CX3CR1 might play a protective role in kidney and liver fibrosis [6, 7]. High expression of chemokine (C-X3-C motif) receptor 1 (CX3CR1) was shown to contribute to the progression of many fibrotic diseases. There is still no study for the role of CX3CR1 in idiopathic pulmonary fibrosis (IPF). We aimed to identify CX3CR1-related immune infiltration genes (IIGs) in IPF and establish a combined risk model to evaluate the prognosis of IPF
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