Role of conventional dendritic cells in schistosomiasis-induced pulmonary hypertension.

IF 7.7 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical science Pub Date : 2025-10-01 DOI:10.1042/CS20256896

Claudia Mickael, Rahul Kumar, Dara C Fonseca Balladares, Kevin Nolan, Michael H Lee, Biruk Kassa, Thais C F Menezes, Anthony Lau-Xiao, Ajaypal Sahota, Linda Sanders, Katie Tuscan, Aneta Gandjeva, Kelly M Cautivo, Ari Molofsky, Brian B Graham

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引用次数: 0

Abstract

Background: Schistosomiasis is a major cause of pulmonary hypertension (PH) worldwide, and CD4 T cells are critical in disease pathogenesis. The role of dendritic cells (DCs) in Schistosoma-induced PH (SchPH) is unknown. There are two types of conventional DCs, cDC1 and cDC2, that prototypically activate CD8 and CD4 T cells, respectively.

Methods: We exposed wildtype, DC reporter, and DC knockout mice to Schistosoma mansoni and quantified PH severity by heart catheterization and cell density by flow cytometry.

Results: Experimental S. mansoni exposure increased the density of pulmonary DCs, particularly cDC2s. Deleting both cDC subsets did not significantly modify SchPH disease severity. Deleting only cDC1s caused more severe SchPH, associated with more Th2 CD4 and CD8 T cells. In contrast, deleting only cDC2s reduced SchPH disease severity.

Conclusions: cDC1s appear to be protective, whereas cDC2s promote disease in SchPH.

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传统树突状细胞在血吸虫病引起的肺动脉高压中的作用。

背景：血吸虫病是世界范围内肺动脉高压（PH）的主要病因，CD4 T细胞在该病发病机制中起关键作用。树突状细胞（dc）在血吸虫诱导的PH （SchPH）中的作用尚不清楚。有两种类型的常规dc， cDC1和cDC2，分别激活CD8和CD4 T细胞。方法：我们将野生型、DC报告型和DC敲除型小鼠暴露于曼氏血吸虫，并通过心导管插管和流式细胞术定量PH严重程度和细胞密度。结果：实验曼梭菌暴露可增加肺dc的密度，尤其是cDC2s。删除两个cDC亚群并没有显著改变SchPH疾病的严重程度。仅删除cDC1s导致更严重的SchPH，与更多的Th2 CD4和CD8 T细胞相关。相比之下，仅删除cDC2s可降低SchPH疾病的严重程度。结论：cDC1s似乎具有保护作用，而cDC2s则促进SchPH的疾病。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical science 医学-医学：研究与实验

CiteScore

11.40

自引率

0.00%

发文量

189

审稿时长

4-8 weeks

期刊介绍： Translating molecular bioscience and experimental research into medical insights, Clinical Science offers multi-disciplinary coverage and clinical perspectives to advance human health. Its international Editorial Board is charged with selecting peer-reviewed original papers of the highest scientific merit covering the broad spectrum of biomedical specialities including, although not exclusively: Cardiovascular system Cerebrovascular system Gastrointestinal tract and liver Genomic medicine Infection and immunity Inflammation Oncology Metabolism Endocrinology and nutrition Nephrology Circulation Respiratory system Vascular biology Molecular pathology.