Sex-specific phenotypical, functional and metabolic profiles of human term placenta macrophages.

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Biology of Sex Differences Pub Date : 2024-10-17 DOI:10.1186/s13293-024-00652-w
Daniel E Paparini, Esteban Grasso, Franco Aguilera, M Agustina Arslanian, Victoria Lella, Brenda Lara, Ana Schafir, Soledad Gori, Fátima Merech, Vanesa Hauk, Claudio Schuster, Marcelo Martí, Cesar Meller, Rosanna Ramhorst, Daiana Vota, Claudia Pérez Leirós
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Abstract

Background: Placental macrophages, Hofbauer cells (HBC) are the only fetal immune cell population within the stroma of healthy placenta along pregnancy. They are central players in maintaining immune tolerance during pregnancy. Immunometabolism emerged a few years ago as a new field that integrates cellular metabolism with immune responses, however, the immunometabolism of HBC has not been explored yet. Here we studied the sex-specific differences in the phenotypic, functional and immunometabolic profile of HBC.

Methods: HBC were isolated from human term placentas (N = 31, 16 from male and 15 female neonates). Ex vivo assays were carried out to assess active metabolic and endoplasmic reticulum stress pathways by flow cytometry, confocal microscopy, gene expression and in silico approaches.

Results: HBC from female placentas displayed a stronger M2 phenotype accompanied by high rates of efferocytosis majorly sustained on lipid metabolism. On the other hand, male HBC expressed a weaker M2 phenotype with higher glycolytic metabolism. LPS stimulation reinforced the glycolytic metabolism in male but not in female HBC. Physiological endoplasmic reticulum stress activates IRE-1 differently, since its pharmacological inhibition increased lipid mobilization, accumulation and efferocytosis only in female HBC. Moreover, differential sex-associated pathways accompanying the phenotypic and functional profiles of HBC appeared related to the placental villi environment.

Conclusions: These results support sex-associated effects on the immunometabolism of the HBC and adds another layer of complexity to the intricate maternal-fetal immune interaction.

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人类足月胎盘巨噬细胞的性别表型、功能和代谢特征。
背景:胎盘巨噬细胞和霍夫鲍尔细胞(HBC)是孕期健康胎盘基质中唯一的胎儿免疫细胞群。它们是维持孕期免疫耐受的核心角色。免疫代谢学是几年前兴起的一个新领域,它将细胞代谢与免疫反应结合在一起,然而,HBC的免疫代谢尚未被研究。方法:从人类足月胎盘中分离出 HBC(31 个,其中 16 个来自男性新生儿,15 个来自女性新生儿)。通过流式细胞术、共聚焦显微镜、基因表达和硅学方法进行体内外检测,以评估活跃的代谢和内质网应激途径:结果:雌性胎盘中的HBC显示出更强的M2表型,并伴随着主要依靠脂质代谢维持的高流出率。另一方面,雄性 HBC 的 M2 表型较弱,糖代谢较高。LPS 刺激加强了雄性 HBC 的糖代谢,而雌性 HBC 则没有。生理内质网应激对 IRE-1 的激活作用不同,因为只有在雌性 HBC 中药物抑制 IRE-1 才会增加脂质动员、积累和排泄。此外,伴随 HBC 表型和功能特征的不同性别相关途径似乎与胎盘绒毛环境有关:这些结果支持了性别对 HBC 免疫代谢的影响,并为错综复杂的母胎免疫相互作用增添了另一层复杂性。
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来源期刊
Biology of Sex Differences
Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY
CiteScore
12.10
自引率
1.30%
发文量
69
审稿时长
14 weeks
期刊介绍: Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.
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