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Th17 cell frequency and IL-17A production in peripheral blood of patients with non-small-cell lung cancer.

ABSTRACT: OBJECTIVE:This study investigated the frequency of T-helper (Th)17 lymphocytes and production of cytokine interleukin (IL)-17 in peripheral blood of patients with non-small-cell lung cancer (NSCLC) and their use as a marker of clinical value. METHODS:Sixty patients with NSCLC and 60 healthy volunteers were enrolled in the study. Flow cytometry was used to detect the frequency of Th17 lymphocytes in peripheral blood, and enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of IL-17. We analyzed the association of Th17 lymphocytes and IL-17 levels in the peripheral blood of patients with their clinicopathological features. RESULTS:Frequency of Th17 lymphocytes and production of IL-17 were significantly higher in the NSCLC group than in the control group and were higher in patients with a smoking history compared with non-smokers. Moreover, Th17 lymphocyte and IL-17 expression levels were higher in patients with squamous cell carcinoma than in patients with adenocarcinoma, and significantly higher in patients with stage III and IV cancers than in patients at stage I or II. CONCLUSION:Th17 lymphocytes and IL-17 play an important role in the development of NSCLC in patients and may have clinical value as markers for treatment of NSCLC.

SUBMITTER: Chen G

PROVIDER: S-EPMC7328058 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Th17 cell frequency and IL-17A production in peripheral blood of patients with non-small-cell lung cancer.

Chen Gang G Zhang Pei-Gang PG Li Jun-Sheng JS Duan Jing-Jing JJ Su Wen W Guo Shi-Ping SP Wang Yan-Feng YF Sun Jun-Ning JN Yang Xiao-Tang XT

The Journal of international medical research 20200601 6

<h4>Objective</h4>This study investigated the frequency of T-helper (Th)17 lymphocytes and production of cytokine interleukin (IL)-17 in peripheral blood of patients with non-small-cell lung cancer (NSCLC) and their use as a marker of clinical value.<h4>Methods</h4>Sixty patients with NSCLC and 60 healthy volunteers were enrolled in the study. Flow cytometry was used to detect the frequency of Th17 lymphocytes in peripheral blood, and enzyme-linked immunosorbent assay (ELISA) was used to detect ...[more]

PMID: 32600079

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Project description:BackgroundStudies have revealed important roles for IL-17A in the development of acute lung injury (ALI) following sepsis. However, the mechanism underlying the regulation of lung IL-17A remains to be fully addressed. Recent studies suggested the effect of neuromedin U (NMU) on immune cell activation and the role of group 2 innate lymphoid cells (ILC2s) in the modulation of IL-17A production. We aimed to gain in-depth insight into the mechanism underlying sepsis-induced lung IL-17A production, particularly, the role of NMU in mediating neuronal regulation of ILC2s and IL-17A-producing γδ T cells activation in sepsis.MethodsWild type mice were subjected to cecal ligation and puncture (CLP) to induce sepsis with or without intraperitoneal injection of NMU. The levels of ILC2s, γδ T cells, IL-17A, NMU and NMU receptor 1 (NMUR1) in the lung were then measured. In order to determine the role of NMU signaling in ILC2 activation and the role of ILC2-released IL-9 in ILC2-γδ T cell interaction, ILC2s were sorted, and the genes of nmur1 and il9 in the ILC2s were knocked down using CRISPR/Cas9. The genetically manipulated ILC2s were then co-cultured with lung γδ T cells, and the levels of IL-17A from co-culture systems were measured.ResultsIn septic mice, the levels of NMU, IL-17A, ILC2s, and IL-17A-producing γδ T cells in the lung are significantly increased, and the expression of NMUR1 in ILC2s is increased as well. Exogenous NMU further augments these increases. The main source of IL-17A in response to CLP is γδ T cells, and lung nmur1 is specifically expressed in ILC2s. In vitro co-culture of ILC2s and γδ T cells leads to increased number of γδ T cells and higher production of IL-17A from γδ T cells, and these alterations are further augmented by septic treatment and exogenous NMU. Genetic knockdown of nmur1 or il9 in ILC2s attenuated the upregulation of γδ T cells and IL-17A production.ConclusionIn sepsis, NMU acting through NMUR1 in lung ILC2s initiates the ILC2 activation, which, in turn, promote IL-17A-producing γδ T cell expansion and secretion of IL-17A. ILC2-derived IL-9 plays an important role in mediating γδ T cell expansion and IL-17A production. This study explores a new mechanism underlying neuronal regulation of innate immunity in sepsis.

Dataset Information

Th17 cell frequency and IL-17A production in peripheral blood of patients with non-small-cell lung cancer.

Publications

Th17 cell frequency and IL-17A production in peripheral blood of patients with non-small-cell lung cancer.

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