肺内 T 细胞足以引起 - 诱导的肺动脉高压。

Intrapulmonary T Cells Are Sufficient for -Induced Pulmonary Hypertension.

机构信息

Lung Biology Center, Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, CA 94110, USA.

Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

出版信息

Int J Mol Sci. 2024 Aug 24;25(17):9202. doi: 10.3390/ijms25179202.

DOI:10.3390/ijms25179202

PMID:39273153

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11395458/

Abstract

BACKGROUND

Schistosomiasis is a parasitic infection that can cause pulmonary hypertension (PH). Th2 CD4 T cells are necessary for experimental -PH. However, if T cells migrate to the lung to initiate, the localized inflammation that drives vascular remodeling and PH is unknown.

METHODS

Mice were sensitized to eggs intraperitoneally and then challenged using tail vein injection. FTY720 was administered, which blocks lymphocyte egress from lymph nodes. T cells were quantified using flow cytometry, PH severity via heart catheterization, and cytokine concentration through ELISA.

RESULTS

FTY720 decreased T cells in the peripheral blood, and increased T cells in the mediastinal lymph nodes. However, FTY720 treatment resulted in no change in PH or type 2 inflammation severity in mice sensitized and challenged with eggs, and the number of memory and effector CD4 T cells in the lung parenchyma was also unchanged. Notably, intraperitoneal egg sensitization alone resulted in a significant increase in intravascular lymphocytes and T cells, including memory T cells, although there was no significant change in parenchymal cell density, IL-4 or IL-13 expression, or PH.

CONCLUSION

Blocking T cell migration did not suppress PH following egg challenge. Memory CD4 T cells, located in the lung intravascular space following egg sensitization, appear sufficient to cause type 2 inflammation and PH.

摘要

背景

血吸虫病是一种寄生虫感染，可导致肺动脉高压（PH）。Th2 CD4 T 细胞是实验性 PH 的必要条件。然而，如果 T 细胞迁移到肺部引发驱动血管重塑和 PH 的局部炎症，则尚不清楚。

方法

用腹腔内注射虫卵使小鼠致敏，然后通过尾静脉注射进行挑战。给予 FTY720，其可阻止淋巴细胞从淋巴结中移出。通过心导管术测量 PH 严重程度，通过 ELISA 测量细胞因子浓度，使用流式细胞术定量 T 细胞。

结果

FTY720 减少了外周血中的 T 细胞，并增加了纵隔淋巴结中的 T 细胞。然而，FTY720 治疗并未改变用虫卵致敏和挑战的小鼠的 PH 或 2 型炎症严重程度，肺实质中的记忆和效应 CD4 T 细胞数量也没有变化。值得注意的是，单独用腹腔内虫卵致敏会导致血管内淋巴细胞和 T 细胞（包括记忆 T 细胞）显著增加，尽管实质细胞密度、IL-4 或 IL-13 表达或 PH 没有显著变化。