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Respiratory infections regulated blood cells IFN-?-PD-L1 pathway in pediatric asthma.

ABSTRACT: BACKGROUND:Respiratory infections, in general, and rhinovirus infection specifically are the main reason for asthma exacerbation in children and programmed cell death protein 1 ligand (PD-L1) expression inhibits T cell responses. OBJECTIVE:Could the interferon (IFN) type I expression in peripheral blood mononuclear cells (PBMCs) improve disease exacerbation in pediatric asthma? RESULTS:Here we found increased level of PD-L1 messenger RNA (mRNA) in total blood cells isolated from preschool children with virus-induced asthma, with lower percentage of forced expiratory volume in 1?second and with high serum levels of the C-reactive-protein. CONCLUSIONS AND CLINICAL RELEVANCE:These data indicate that, in the presence of infection in the airways of preschool children, worse asthma is associated with induced PD-L1 mRNA expression in blood cells. Further, type I IFN, IFN-?, a cytokine that is involved in the clearance of infections, was found to be associated with a better lung function in asthmatic children. These data suggest that improving peripheral blood IFN type I expression in PBMCs in pediatric asthma could improve disease exacerbation due to suppressing PD-L1 expression in blood cells.

SUBMITTER: Kolle J

PROVIDER: S-EPMC7416032 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Respiratory infections regulated blood cells IFN-β-PD-L1 pathway in pediatric asthma.

Kölle Julia J Haag Patricia P Vuorinen Tytti T Alexander Kiefer K Rauh Manfred M Zimmermann Theodor T Papadopoulos Nikolaos G NG Finotto Susetta S

Immunity, inflammation and disease 20200512 3

<h4>Background</h4>Respiratory infections, in general, and rhinovirus infection specifically are the main reason for asthma exacerbation in children and programmed cell death protein 1 ligand (PD-L1) expression inhibits T cell responses.<h4>Objective</h4>Could the interferon (IFN) type I expression in peripheral blood mononuclear cells (PBMCs) improve disease exacerbation in pediatric asthma?<h4>Results</h4>Here we found increased level of PD-L1 messenger RNA (mRNA) in total blood cells isolated ...[more]

PMID: 32394602

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Project description:BackgroundPD-L1 is an immune inhibitory receptor ligand that leads to T cell dysfunction and apoptosis by binding to its receptor PD-1, which works in braking inflammatory response and conspiring tumor immune evasion. However, in gliomas, the cause of PD-L1 expression in the tumor microenvironment is not yet clear. Besides, auxiliary biomarkers are urgently needed for screening possible responsive glioma patients for anti-PD-1/PD-L1 therapies.MethodsThe distribution of tumor-infiltrating T cells and PD-L1 expression was analyzed via immunofluorescence in orthotopic murine glioma model. The expression of PD-L1 in immune cell populations was detected by flow cytometry. Data excavated from TCGA LGG/GBM datasets and the Ivy Glioblastoma Atlas Project was used for in silico analysis of the correlation among genes and survival.ResultsThe distribution of tumor-infiltrating T cells and PD-L1 expression, which parallels in murine orthotopic glioma model and human glioma microdissections, was interrelated. The IFN-γ level was positively correlated with PD-L1 expression in murine glioma. Further, IFN-γ induces PD-L1 expression on primary cultured microglia, bone marrow-derived macrophages, and GL261 glioma cells in vitro. Seven IFN-γ-induced genes, namely GBP5, ICAM1, CAMK2D, IRF1, SOCS3, CD44, and CCL2, were selected to calculate as substitute indicator for IFN-γ level. By combining the relative expression of the listed IFN-γ-induced genes, IFN-γ score was positively correlated with PD-L1 expression in different anatomic structures of human glioma and in glioma of different malignancies.ConclusionOur study identified the distribution of tumor-infiltrating T cells and PD-L1 expression in murine glioma model and human glioma samples. And we found that IFN-γ is an important cause of PD-L1 expression in the glioma microenvironment. Further, we proposed IFN-γ score aggregated from the expressions of the listed IFN-γ-induced genes as a complementary prognostic indicator for anti-PD-1/PD-L1 therapy.

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Respiratory infections regulated blood cells IFN-?-PD-L1 pathway in pediatric asthma.

Publications

Respiratory infections regulated blood cells IFN-β-PD-L1 pathway in pediatric asthma.

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