IL-17C 介导体细胞极化在中性粒细胞性哮喘 17 型炎症中的作用。

Contribution of IL-17C-mediated macrophage polarization to Type 17 inflammation in neutrophilic asthma.

机构信息

The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The Second Affiliated Hospital, Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, 510260, China.

Department of Hematology, Guangzhou First People's HospitalInstitute of Blood Transfusion and Hematology, Guangzhou Medical University, Guangzhou, Guangdong, China.

出版信息

Cell Commun Signal. 2024 Nov 21;22(1):557. doi: 10.1186/s12964-024-01937-8.

DOI:10.1186/s12964-024-01937-8

PMID:39568050

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11580697/

Abstract

BACKGROUND

IL-17C has been described in a variety of inflammatory diseases driven by neutrophils. However, the role of IL-17C in neutrophilic asthma has not been completely characterized.

METHODS

The level of IL-17C in asthmatic patients and mice was assessed. Il-17c-deficient mice or mice treated with exogenous rmIL-17C were performed for OVA/CFA-induced asthmatic mice model. Pulmonary inflammation was evaluated by histological analysis, flow cytometry and cytokine analysis. Il-17re-overexpressed Raw264.7 were used in vitro to investigate the role of IL-17C in macrophage polarization.

RESULTS

Here, we show IL-17C were increased in serum or plasma from asthmatic patients and OVA/CFA-induced asthma mice. In the OVA/CFA-induced model, exogenous rmIL-17C aggravated neutrophil- and Type 17-dominated inflammation and promoted M1 macrophage differentiation, whereas deficiency of Il-17c reversed the pro-inflammatory phenotypes and inhibited the expansion of M1 macrophages. In vitro, IL-17C in synergy with IFN-γ induced STAT1 activation in Il-17re overexpressed Raw264.7 to upregulate M1-related genes expression, and promoted pro-inflammatory M1 polymerization, whereas IL-17C in contrast to the effect of IL-4 inhibited STAT6 activation, to reduce Raw264.7 differentiation to M2 macrophage and functional M2-related genes expression.

CONCLUSIONS

IL-17C promotes allergic inflammation via M1 polarization of pulmonary macrophages in neutrophilic asthma. Modulation of the IL-17C/IL-17RE axis represents a novel therapeutic target in neutrophilic asthma.

摘要

背景

IL-17C 已在多种由中性粒细胞驱动的炎症性疾病中被描述。然而，IL-17C 在中性粒细胞性哮喘中的作用尚未完全阐明。

方法

评估哮喘患者和小鼠中 IL-17C 的水平。进行 Il-17c 缺陷小鼠或用外源性 rmIL-17C 处理的小鼠的 OVA/CFA 诱导的哮喘小鼠模型。通过组织学分析、流式细胞术和细胞因子分析评估肺部炎症。体外使用过表达 Il-17re 的 Raw264.7 来研究 IL-17C 在巨噬细胞极化中的作用。

结果

在这里，我们显示 IL-17C 在哮喘患者的血清或血浆中或在 OVA/CFA 诱导的哮喘小鼠中增加。在 OVA/CFA 诱导的模型中，外源性 rmIL-17C 加重了中性粒细胞和 17 型为主的炎症，并促进了 M1 巨噬细胞分化，而 Il-17c 的缺乏则逆转了促炎表型并抑制了 M1 巨噬细胞的扩增。在体外，IL-17C 与 IFN-γ 协同作用在 Il-17re 过表达的 Raw264.7 中诱导 STAT1 激活，以上调 M1 相关基因的表达，并促进促炎 M1 聚合，而 IL-17C 与 IL-4 的作用相反抑制 STAT6 激活，从而减少 Raw264.7 分化为 M2 巨噬细胞和功能性 M2 相关基因的表达。