NFIL3/Tim3 axis regulates effector Th1 inflammation in COPD mice

作者：Junyi Ke, Shu Huang, Zhixiong He, Siyu Lei, Shiya Lin, Yinying Li, Qiuming Li, Hui Huang, Hongchun Huang, Huajiao Qin, Minchao Duan · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1482213 · 被引用次数：8 · 研究领域：Galectins and Cancer Biology、Signaling Pathways in Disease、Inflammation biomarkers and pathways

Background IFN-γ+CD4+ cells (type 1 helper T cells, Th1) represent a critical component of the inflammatory environment in the lungs of chronic obstructive pulmonary disease (COPD). Identifying influencing factors related to COPD-associated Th1 cells will enhance our understanding of the inflammatory mechanisms involved and facilitate the development of targeted interventions. Method We describe T-cell immunoglobulin and mucin-domain containing-3 (Tim3) as a key gene regulating COPD-associated Th1 cells through single-cell sequencing, flow cytometry and knockout mice. Results Our findings indicate that Havcr2 expression gradually increases during CD4+ T cell activation in COPD mice, with Tim3 being highly expressed on both CD4+ T cells and Th1 cells. Notably, the knockout of HAVCR2 further promotes the infiltration of CD4+ T cells and the expression of IFN-γ in the lungs, resulting in a more severe emphysema phenotype, although it does not significantly affect TNF-α expression. Additionally, NFIL3, an upstream regulator of Tim3, is also highly expressed in the CD4+ T cells of COPD mice. Mice with NFIL3 knockout exhibit phenotypes similar to those of HAVCR2 knockout mice, along with a significant downregulation of Tim3 expression. In vitro , we simulated the activation process by polarizing primary CD4+ Tn cells from COPD mice and observed that NFIL3/Tim3 expression was significantly upregulated following Th1 polarization. Conclusion Our study demonstrates that the NFIL3/Tim3 ...