scholarly journals Investigation of a Hypoxia-Immune-Related Microenvironment Gene Signature and Prediction Model for Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinyu Li ◽  
Haozheng Cai ◽  
Yufeng Cai ◽  
Quyan Zhang ◽  
Yinghe Ding ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Peripheral Blood Mononuclear Cell ◽  
Prediction Model ◽  
Peripheral Blood ◽  
Immune Status ◽  
Peripheral Blood Mononuclear ◽  
Independent Validation ◽  
Geo Database

BackgroundThere is growing evidence found that the role of hypoxia and immune status in idiopathic pulmonary fibrosis (IPF). However, there are few studies about the role of hypoxia and immune status in the lung milieu in the prognosis of IPF. This study aimed to develop a hypoxia-immune-related prediction model for the prognosis of IPF.MethodsHypoxia and immune status were estimated with microarray data of a discovery cohort from the GEO database using UMAP and ESTIMATE algorithms respectively. The Cox regression model with the LASSO method was used for identifying prognostic genes and developing hypoxia-immune-related genes. Cibersort was used to evaluate the difference of 22 kinds of immune cell infiltration. Three independent validation cohorts from GEO database were used for external validation. Peripheral blood mononuclear cell (PBMC) and bronchoalveolar lavage fluid (BALF) were collected to be tested by Quantitative reverse transcriptase-PCR (qRT-PCR) and flow cytometry from 22 clinical samples, including 13 healthy controls, six patients with non-fibrotic pneumonia and three patients with pulmonary fibrosis.ResultsHypoxia and immune status were significantly associated with the prognosis of IPF patients. High hypoxia and high immune status were identified as risk factors for overall survival. CD8+ T cell, activated CD4+ memory T cell, NK cell, activated mast cell, M1 and M0 macrophages were identified as key immune cells in hypoxia-immune-related microenvironment. A prediction model for IPF prognosis was established based on the hypoxia-immune-related one protective and nine risk DEGs. In the independent validation cohorts, the prognostic prediction model performed the significant applicability in peripheral whole blood, peripheral blood mononuclear cell, and lung tissue of IPF patients. The preliminary clinical specimen validation suggested the reliability of most conclusions.ConclusionsThe hypoxia-immune-based prediction model for the prognosis of IPF provides a new idea for prognosis and treatment.

scholarly journals Peripheral blood myeloid-derived suppressor cells reflect disease status in idiopathic pulmonary fibrosis

2016 ◽  
Vol 48 (4) ◽  
pp. 1171-1183 ◽  
Author(s):  
Isis E. Fernandez ◽  
Flavia R. Greiffo ◽  
Marion Frankenberger ◽  
Julia Bandres ◽  
Katharina Heinzelmann ◽  
...  
Keyword(s):  
T Cell ◽  
Lung Function ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Peripheral Blood ◽  
Suppressor Cells ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Myeloid Derived Suppressor Cells ◽  
Peripheral Blood Mononuclear

Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative disease with irreversible lung function loss and poor survival. Myeloid-derived suppressor cells (MDSC) are associated with poor prognosis in cancer, facilitating immune evasion. The abundance and function of MDSC in IPF is currently unknown.Fluorescence-activated cell sorting was performed in 170 patients (IPF: n=69; non-IPF interstitial lung disease (ILD): n=56; chronic obstructive pulmonary disease (COPD): n=23; healthy controls: n=22) to quantify blood MDSC and lymphocyte subtypes. MDSC abundance was correlated with lung function, MDSC localisation was performed by immunofluorescence. Peripheral blood mononuclear cell (PBMC) mRNA levels were analysed by qRT-PCR.We detected increased MDSC in IPF and non-IPF ILD compared with controls (30.99±15.61% versus 18.96±8.17%, p≤0.01). Circulating MDSC inversely correlated with maximum vital capacity (r= −0.48, p≤0.0001) in IPF, but not in COPD or non-IPF ILD. MDSC suppressed autologous T-cells. The mRNA levels of co-stimulatory T-cell signals were significantly downregulated in IPF PBMC. Importantly, CD33+CD11b+ cells, suggestive of MDSC, were detected in fibrotic niches of IPF lungs.We identified increased MDSC in IPF and non-IPF ILD, suggesting that elevated MDSC may cause a blunted immune response. MDSC inversely correlate with lung function only in IPF, identifying them as potent biomarkers for disease progression. Controlling expansion and accumulation of MDSC, or blocking their T-cell suppression, represents a promising therapy in IPF.

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