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PTX3在终末淋巴管中表达,并塑造其组织结构和功能。

PTX3 is expressed in terminal lymphatics and shapes their organization and function.

作者信息

Doni Andrea, Sironi Marina, Del Prete Annalisa, Pasqualini Fabio, Valentino Sonia, Cuccovillo Ivan, Parente Raffaella, Calvi Michela, Tosoni Antonella, Vago Gianluca, Nebuloni Manuela, Garlanda Cecilia, Vecchi Annunciata, Bottazzi Barbara, Mantovani Alberto

机构信息

Unit of Multiscale and Nanostructural Imaging, IRCCS Humanitas Research Hospital, Milan, Italy.

Cellular and Humoral Innate Immunity Lab, IRCCS Humanitas Research Hospital, Milan, Italy.

出版信息

Front Immunol. 2024 Nov 21;15:1426869. doi: 10.3389/fimmu.2024.1426869. eCollection 2024.

Abstract

INTRODUCTION

The lymphatic system is a multifaceted regulator of tissue homeostasis and an integral part of immune responses. Previous studies had shown that subsets of lymphatic endothelial cells (LEC) express , an essential component of humoral innate immunity and tissue homeostasis.

METHODS

In the present study using whole-mount imaging and image-based morphometric quantifications, -targeted mice and functional analysis, we investigated the involvement of PTX3 in shaping and function of the lymphatic vasculature.

RESULTS

We found that PTX3 is localized in the extracellular matrix (ECM) surrounding human and murine lymphatic vessels (LV). In murine tissues, PTX3 was localized in the ECM close to LV terminals and sprouting. -deficient mice showed LV abnormalities in the colon submucosa and diaphragm, including a disorganized pattern and hyperplasia of initial LV capillaries associated with altered distribution of tight junction-associated molecules. Mice with LEC-restricted PTX3 gene inactivation showed morphological and organization abnormalities similar to those observed in -deficient animals. Ptx3-deficient mice showed defective fluid drainage from footpads and defective dendritic cell (DC) trafficking.

DISCUSSION

Thus, PTX3 is strategically localized in the ECM of specialized LV, playing an essential role in their structural organization and immunological function.

摘要

引言

淋巴系统是组织稳态的多方面调节者,也是免疫反应的重要组成部分。先前的研究表明,淋巴内皮细胞(LEC)亚群表达 ,这是体液固有免疫和组织稳态的重要组成部分。

方法

在本研究中,我们使用整体成像和基于图像的形态计量学量化、靶向小鼠和功能分析,研究了PTX3在淋巴管系统形成和功能中的作用。

结果

我们发现PTX3定位于人和小鼠淋巴管(LV)周围的细胞外基质(ECM)中。在小鼠组织中,PTX3定位于靠近LV末端和萌芽处的ECM中。缺乏 的小鼠在结肠黏膜下层和膈肌中表现出LV异常,包括初始LV毛细血管的紊乱模式和增生,这与紧密连接相关分子的分布改变有关。淋巴管内皮细胞特异性PTX3基因失活的小鼠表现出与缺乏 动物中观察到的相似的形态和组织异常。缺乏Ptx3的小鼠表现出脚垫液体引流缺陷和树突状细胞(DC)运输缺陷。

讨论

因此,PTX3战略性地定位于特殊LV的ECM中,在其结构组织和免疫功能中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7611/11617523/43841972cd03/fimmu-15-1426869-g001.jpg

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