Matrix Biology最新文献_第4页

Heparan sulfate N-deacetylase/N-sulfotransferase-1 regulates glioblastoma cell migration and invasion 硫酸乙酰肝素n -去乙酰化酶/ n -硫转移酶-1调控胶质母细胞瘤细胞的迁移和侵袭。

IF 4.8 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Matrix Biology

Pub Date : 2025-08-10 DOI: 10.1016/j.matbio.2025.08.003

Argyris Spyrou , Ananya Roy , Anqi Xiong , Soumi Kundu , Xi Lu , Ylva Jansson , Anna Falk , Christoph Riethmüller , Burkhard Greve , Martin Götte , Xinqi Chen , Lena Kjellén , Karin Forsberg-Nilsson

The glioblastoma (GBM) microenvironment undergoes adaptations to support tumor progression, including a dysregulated extracellular matrix, with altered heparan sulfate (HS) proteoglycans. We investigated N-deacetylase/N-sulfotransferase-1 (NDST1) because NDSTs are initial modifying enzymes of HS biosynthesis and have key roles in designing the HS sulfation pattern. This, in turn governs interactions with growth factors and other biomolecules. We report that NDST1 expression is lower in GBM than in the normal brain, and that patient-derived GBM cells, grown under neural stem cell culture conditions have lower levels of HS than normal astrocytes. Overexpression of NDST1 in GBM cells with low inherent NDST1 levels stimulates cell migration, reduce cell adhesion, induce EMT markers and increase invasion. Conversely, when NDST1 levels were reduced by shRNA in GBM cells, that had higher baseline expression, we find that invasion is reduced, and instead, self-renewal capacity increases alongside elevated stem cell marker expression. Moreover, overexpression of NDST1 changes chromatin accessibility of gene regulatory regions with the capacity to affect transcription factor expression, and pathways that favors cell motility and invasion. Furthermore, NDST1 overexpression results in increased activation of several receptor tyrosine kinases. This study shows that low NDST1 levels support GBM cell stemness, whereas high NDST1 levels endow tumor cells with a motile cell phenotype. We therefore propose that NDST1 is important for regulation of the balance between proliferation and invasive properties in GBM cells.

胶质母细胞瘤（GBM）微环境经历适应以支持肿瘤进展，包括细胞外基质失调，硫酸肝素（HS）蛋白聚糖改变。我们研究了n -去乙酰化酶/ n -硫转移酶-1 (NDST1)，因为NDST1是HS生物合成的初始修饰酶，在设计HS磺化模式中起关键作用。这反过来又控制着与生长因子和其他生物分子的相互作用。我们报道了NDST1在GBM中的表达低于正常大脑，并且在神经干细胞培养条件下生长的患者来源的GBM细胞的HS水平低于正常星形胶质细胞。NDST1在固有NDST1水平较低的GBM细胞中过表达，可刺激细胞迁移，降低细胞粘附，诱导EMT标志物，增加侵袭。相反，当具有较高基线表达的GBM细胞中的NDST1水平被shRNA降低时，我们发现侵袭减少，相反，自我更新能力随着干细胞标记物表达的升高而增加。此外，NDST1的过表达改变了基因调控区域的染色质可及性，从而影响转录因子的表达，以及有利于细胞运动和侵袭的途径。此外，NDST1过表达导致几种受体酪氨酸激酶的激活增加。该研究表明，低NDST1水平支持GBM细胞的干性，而高NDST1水平赋予肿瘤细胞运动细胞表型。因此，我们认为NDST1在GBM细胞增殖和侵袭特性之间的平衡调节中很重要。

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引用次数: 0

Basement membranes in lung development, disease, and repair 基底膜在肺发育、疾病和修复中的作用。

IF 4.8 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Matrix Biology

Pub Date : 2025-07-28 DOI: 10.1016/j.matbio.2025.07.007

Matilda Thuringer , Roy Zent , Rachel Lennon , Erin J. Plosa

The primary function of the respiratory system is the exchange of oxygen and carbon dioxide across the alveolar-capillary barrier in the distal lung. This structure is composed of alveolar epithelial cells (type 1 and type 2) and capillary endothelial cells, separated by a thin, fused alveolar basement membrane. The developmental programming that creates this specialized niche is largely unexplored and the role of lung basement membranes in respiratory disease pathogenesis and repair remains an emerging field of study. Thus, in this review, we discuss the distribution, composition, and function of the alveolar basement membrane, as well as the other three lung basement membranes that support the airway epithelium, airway smooth muscles, and the endothelium of the macrovasculature in lung development and disease.

呼吸系统的主要功能是通过远端肺的肺泡-毛细血管屏障交换氧气和二氧化碳。该结构由肺泡上皮细胞（1型和2型）和毛细血管内皮细胞组成，由一层薄薄的融合肺泡基底膜隔开。创造这种特殊生态位的发育程序在很大程度上尚未被探索，肺基底膜在呼吸系统疾病发病机制和修复中的作用仍然是一个新兴的研究领域。因此，在这篇综述中，我们讨论了肺泡基底膜的分布、组成和功能，以及在肺发育和疾病中支持气道上皮、气道平滑肌和大血管内皮的其他三种肺基底膜。

引用次数: 0

Collagen diversity in human skin: Aging, wound healing, and disorders 胶原蛋白在人类皮肤的多样性：老化，伤口愈合和疾病。

IF 4.8 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Matrix Biology

Pub Date : 2025-07-25 DOI: 10.1016/j.matbio.2025.07.006

Mélanie Salamito , Valérie Haydont , Hervé Pageon , Florence Ruggiero , Sarah Girardeau-Hubert

Collagen is an essential skin protein, accounting for 75 % of the skin’s dry weight. The collagen superfamily encompasses a diverse group of proteins with a variety of structures that fulfil a wide range of functions. The half-life of collagen in the skin is generally estimated at 10 to 15 years; however, the expression pattern of the different types of skin collagen varies throughout life. Both intrinsic and extrinsic factors influence collagen turn-over within the different skin layers. In this review, we discuss current knowledge of the different types of collagen present in human skin, focusing on insights gained from research exploring the dynamic roles of these proteins in skin development, homeostasis including aging, collagen-linked pathologies, adaptability in response to stress, and wound healing-related processes and disorders. Specificities of skin diversity due to ancestral origin and gender will also be discussed.

胶原蛋白是一种重要的皮肤蛋白质，占皮肤干重的75%。胶原蛋白超家族包括一组具有多种结构的蛋白质，这些蛋白质具有广泛的功能。皮肤中胶原蛋白的半衰期一般估计为10至15年；然而，不同类型的皮肤胶原蛋白的表达模式在人的一生中是不同的。内在和外在因素都会影响不同皮肤层内的胶原蛋白周转。在这篇综述中，我们讨论了目前对人类皮肤中不同类型胶原蛋白的了解，重点介绍了这些蛋白质在皮肤发育、体内平衡（包括衰老）、胶原相关病理、应激适应性以及伤口愈合相关过程和疾病中的动态作用。由于祖先起源和性别的皮肤多样性的特殊性也将被讨论。

引用次数: 0

Drosophila Col4a1 Glycine mutations highlight allelic heterogeneity and mechanistic pleiotropy 果蝇Col4a1甘氨酸突变突出了等位基因异质性和机制多效性。

IF 4.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Matrix Biology

Pub Date : 2025-07-22 DOI: 10.1016/j.matbio.2025.07.005

Angus Nichols, Besaiz J. Sánchez-Sánchez, Stefania Marcotti, María-del-Carmen Díaz-de-la-Loza, Leonel C. Menezes, Tingfei Wang, Robert M. Johnson, Brian M. Stramer

Collagen IV (Col4) is a heterotrimer containing a triple helical domain broken up by short interruptions. Mutation of Glycine residues within the Glycine-X-Y triple helical repeat leads to genetically dominant disease in humans that affects multiple organ systems. Mouse and cell culture-based models have revealed allelic heterogeneity, resulting in a range of Col4 secretion defects depending on the position of the mutation. However, genetic background also affects phenotypic severity, making it challenging to understand the precise underlying molecular mechanisms driving disease. Here, we characterize an allelic series of dominant temperature-sensitive Drosophila Glycine mutations to identify the potential molecular mechanisms driving phenotypic heterogeneity. Analysis of developmental viability at the non-permissive temperature revealed that mutations show a range of developmental lethality that is not correlated with their position within the triple helix nor with the degree of Col4 secretion defect. Backcrossing the series of fly lines led to increased lethality for almost all alleles, highlighting the presence of genetic modifiers, which paradoxically led to a reduction in secretion defects; this further suggests that defective secretion cannot explain the allelic heterogeneity in mutant viability. Analysis of the Col4 network surrounding the central nervous system (CNS) revealed that Glycine mutations can also affect basement membrane (BM) structure and alter its mechanical properties. Additionally, fluorescent tagging of a Glycine mutant variant showed that the mutated trimer is sufficiently secreted and can be incorporated into the network to dominantly affect BM organization. These data reveal that Col4 Glycine mutations can cause both secretion and direct BM network defects, suggesting that Col4-related pathologies may be mechanistically pleiotropic.

胶原IV （Col4）是一种含有三螺旋结构域的异源三聚体，该结构域由短中断断开。甘氨酸- x - y三螺旋重复序列中甘氨酸残基的突变导致人类遗传显性疾病，影响多器官系统。基于小鼠和细胞培养的模型揭示了等位基因的异质性，导致Col4分泌缺陷的范围取决于突变的位置。然而，遗传背景也会影响表型的严重程度，这使得理解驱动疾病的精确潜在分子机制具有挑战性。在这里，我们描述了一系列显性温度敏感的果蝇甘氨酸突变的等位基因，以确定驱动表型异质性的潜在分子机制。在非允许温度下的发育活力分析表明，突变显示出一系列的发育致死率，这与它们在三螺旋中的位置无关，也与Col4分泌缺陷的程度无关。蝇系系列的回交导致几乎所有等位基因的致死率增加，突出了遗传修饰的存在，这矛盾地导致了分泌缺陷的减少；这进一步表明分泌缺陷不能解释突变体活力的等位基因异质性。对中枢神经系统（CNS）周围Col4网络的分析表明，甘氨酸突变也可以影响基底膜（BM）结构并改变其力学性能。此外，甘氨酸突变变体的荧光标记表明，突变的三聚体分泌充足，可以被纳入网络，主要影响BM组织。这些数据表明Col4甘氨酸突变既可以引起分泌缺陷，也可以引起直接的BM网络缺陷，这表明Col4相关的病理可能是多效性的。

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引用次数: 0

ECM proteins shape topographical patterns in the basement membrane of Drosophila wing discs ECM蛋白在果蝇翅盘基底膜中形成地形模式

IF 4.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Matrix Biology

Pub Date : 2025-07-15 DOI: 10.1016/j.matbio.2025.06.003

K. Yanín Guerra Santillán, Christian Dahmann, Elisabeth Fischer-Friedrich

The basal surface of epithelial tissues is attached to a thin network of macromolecules known as the basement membrane. The core components of the basement membrane — Collagen IV, Laminin, Perlecan, and Nidogen — are conserved extracellular matrix (ECM) proteins across species. However, the topography of basement membranes and the contribution of individual core components to its establishment remain poorly understood. Here, we used AFM-aided PeakForce tapping to analyze the topography of the basement membrane of Drosophila larval wing discs. We identified a self-affine surface topography, appearing structurally similar across multiple scales. Further, the topography is characterized by thin fiber-like structures that are intermittently aligned with a preferred orientation along the anterior-posterior axis. During larval development, the amplitude of surface patterns overall decreases, whereas the abundance of basement membrane components increases. Using targeted knockdown experiments, we show that Collagen IV is essential for the formation of fiber-like structures, while Laminin and Collagen IV appear to smooth or level out large-scale groove-like patterns. In contrast, Nidogen contributes to the maintenance of these grooves, and Perlecan increases surface pattern amplitudes at all length scales. Our findings reveal distinct topographical features in the basement membrane, whose amplitude and organization depend on its specific molecular composition.

上皮组织的基底表面附着着一层称为基底膜的大分子薄网络。基底膜的核心成分-胶原IV，层粘连蛋白，Perlecan和Nidogen -是跨物种保守的细胞外基质（ECM）蛋白。然而，基底膜的地形和单个核心成分对其建立的贡献仍然知之甚少。在此，我们使用afm辅助PeakForce攻丝对果蝇幼虫翅盘基底膜的形貌进行了分析。我们确定了一个自仿射表面形貌，在多个尺度上出现结构相似。此外，地形的特征是薄的纤维状结构，沿着前后轴间歇性地以首选方向排列。在幼虫发育过程中，表面图案的幅度总体下降，而基底膜成分的丰度增加。通过靶向敲除实验，我们发现胶原蛋白IV对于纤维样结构的形成至关重要，而层粘连蛋白和胶原蛋白IV似乎可以平滑或平整大规模的沟槽样结构。相比之下，氮气有助于维持这些凹槽，而Perlecan则增加了所有长度尺度上的表面图案振幅。我们的发现揭示了基底膜的独特地形特征，其振幅和组织取决于其特定的分子组成。

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引用次数: 0

Role of extracellular space and matrix remodeling in cardiac amyloidosis 细胞外空间和基质重塑在心脏淀粉样变性中的作用

IF 4.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Matrix Biology

Pub Date : 2025-07-14 DOI: 10.1016/j.matbio.2025.07.004

Francesca Lavatelli , Loredana Marchese , Palma Patrizia Mangione , Sara Raimondi , Diana Canetti , Guglielmo Verona , Lucia Venneri , Eloisa Arbustini , Laura Obici , Alessandra Corazza , Vittorio Bellotti , Sofia Giorgetti

The hallmark of amyloid diseases is deposition of misfolded proteins as amyloid fibrils in the interstitium of target organs. Amyloid deposits surround cells, distorting the micro and macro-architecture of the extracellular space and profoundly changing the physical and molecular properties of this compartment. In the heart, extracellular matrix (ECM) remodeling has a profound impact on the mechanical properties of this target organ and on the physiology and metabolism of resident cells. This review critically summarizes the available knowledge on ECM alterations in cardiac amyloidosis, with the goal of providing an overview on how biochemical, biophysical and anatomical modifications are interrelated, and how ECM remodeling participates in the pathophysiology of this unique type of cardiopathy.

淀粉样蛋白疾病的标志是错误折叠的蛋白作为淀粉样原纤维沉积在靶器官间质中。淀粉样蛋白沉积在细胞周围，扭曲了细胞外空间的微观和宏观结构，并深刻地改变了细胞外空间的物理和分子特性。在心脏中，细胞外基质（extracellular matrix， ECM）重构对靶器官的力学特性以及常驻细胞的生理和代谢具有深远的影响。这篇综述批判性地总结了心肌淀粉样变性中ECM改变的现有知识，目的是概述生化，生物物理和解剖改变是如何相互关联的，以及ECM重塑如何参与这种独特类型的心脏病的病理生理学。

引用次数: 0

Building basement membranes with computational approaches 用计算方法构建基底膜。

IF 4.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Matrix Biology

Pub Date : 2025-07-09 DOI: 10.1016/j.matbio.2025.07.001

Alana Stevenson Harris , Rachel Lennon , Jean-Marc Schwartz

Basement membranes (BMs) are dense extracellular matrix scaffolds that support cells. Their composition, structure and dynamic regulation are vital for tissue health and altered in human disease. The expansion of experimental and analytical techniques has generated large multiomic datasets that include BM components; however, the organising principles of BM component assembly and the regulation of BMs remain poorly understood. There are over 160 curated BM proteins, including core, ubiquitous components such as type IV collagen and laminin isoforms, as well as tissue-restricted components, and there is increasing experimental evidence of BM protein-protein interactions. Here we describe and compare multiomic, protein-protein interaction, and BM curation databases and discuss the application of systems biology approaches including network analysis, Boolean networks and Ordinary Differential Equations to integrate data and model BM organisation. Applying computational modelling strategies to BM datasets may reveal unknown organising principles of BM assembly and regulation and predict mechanisms of dysregulation in BM-associated diseases.

基底膜（BMs）是致密的细胞外基质支架，支持细胞。它们的组成、结构和动态调节对组织健康和人类疾病的改变至关重要。实验和分析技术的扩展产生了包括BM成分的大型多组数据集；然而，BM组件组装的组织原则和BM的调节仍然知之甚少。目前有超过160种BM蛋白，包括核心成分，普遍存在的成分，如IV型胶原蛋白和层粘连蛋白异构体，以及组织限制性成分，并且越来越多的实验证据表明BM蛋白与蛋白质相互作用。在这里，我们描述和比较多组学、蛋白质-蛋白质相互作用和BM管理数据库，并讨论系统生物学方法的应用，包括网络分析、布尔网络和常微分方程，以整合数据和建模BM组织。将计算建模策略应用于脑基数据集可以揭示脑基组装和调节的未知组织原理，并预测脑基相关疾病的失调机制。

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引用次数: 0

Around the collagen triple helix: an introduction to studying associated genetic and acquired diseases 围绕胶原蛋白三螺旋：介绍研究相关的遗传和获得性疾病。

IF 4.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Matrix Biology

Pub Date : 2025-07-07 DOI: 10.1016/j.matbio.2025.07.003

Sergei P. Boudko

The triple helix structure of collagen is the most abundant motif found in our bodies. It is believed to have emerged during the transition from unicellular to multicellular animal organisms, known as metazoans, and has evolved into various proteins that contribute to the development and function of diverse animal tissues, organs, and systems. Once synthesized, these collagenous proteins undergo post-translational modifications and proper folding inside the cell, after which they primarily function outside the cell. Over 80 collagenous proteins are categorized into two main groups: collagens and collagen-like proteins. However, the distinction between these groups is not clearly defined. Within these categories, there are various types of proteins, including soluble proteins, transmembrane proteins, and those that form the extracellular matrix. Multiple genetic diseases highlight the significance of collagenous proteins, which can be affected by defects in their primary structure, post-translational modifications, or complete loss. While fixing the gene defect may seem like a straightforward solution, we currently lack the capability to do so. Moreover, acquired diseases caused or accompanied by adverse processes in the collagen triple helix are generally not suitable for gene therapy at all. Understanding the pathogenicity of a defective polypeptide chain can provide valuable insights into strategies for mitigating negative consequences for both genetic and acquired diseases. This review highlights the current state of research in the collagen triple helix field, offering insights into how to study specific defects and deepen our understanding of their underlying pathogenic mechanisms.

胶原蛋白的三螺旋结构是我们体内发现的最丰富的基序。它被认为是在从单细胞动物有机体向多细胞动物有机体过渡的过程中出现的，被称为后生动物，并已进化成各种蛋白质，这些蛋白质有助于各种动物组织、器官和系统的发育和功能。一旦合成，这些胶原蛋白在细胞内进行翻译后修饰和适当折叠，之后它们主要在细胞外发挥作用。超过80种胶原蛋白被分为两大类：胶原蛋白和胶原样蛋白。然而，这些群体之间的区别并没有明确界定。在这些类别中，有各种类型的蛋白质，包括可溶性蛋白质，跨膜蛋白质和那些形成细胞外基质的蛋白质。多种遗传疾病突出了胶原蛋白的重要性，胶原蛋白可能受到其初级结构缺陷、翻译后修饰或完全丢失的影响。虽然修复基因缺陷似乎是一个直截了当的解决方案，但我们目前缺乏这样做的能力。此外，由胶原蛋白三螺旋不良过程引起或伴随的获得性疾病，一般根本不适合进行基因治疗。了解缺陷多肽链的致病性可以为减轻遗传和获得性疾病的负面后果提供有价值的见解。本文综述了胶原蛋白三螺旋领域的研究现状，为如何研究特定缺陷和加深对其潜在致病机制的理解提供了新的见解。

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引用次数: 0

Collagen IV biosynthesis: Intracellular choreography of post-translational modifications 胶原IV型生物合成：翻译后修饰的细胞内编排。

IF 4.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Matrix Biology

Pub Date : 2025-07-04 DOI: 10.1016/j.matbio.2025.07.002

Yoshihiro Ishikawa , Rachel Lennon , Federico Forneris , Johanna Myllyharju , Antti M. Salo

Collagen IV, an essential and evolutionarily conserved component of basement membranes, is one of the most extensively post-translationally modified proteins. Despite substantial research on fibrillar collagen biosynthesis, our understanding of collagen IV biosynthesis, including its post-translational modifications (PTMs), remains limited. Most PTMs occur intracellularly, primarily within the endoplasmic reticulum (ER). In this review, we examine the molecular ensemble that orchestrates collagen IV biosynthesis in the ER, highlighting the complex interplay between prolyl and lysyl hydroxylases, glycosyltransferases, and molecular chaperones. Furthermore, we discuss how defects in collagen IV and its PTMs contribute to various human pathologies, including Gould and Alport syndromes, fibrosis, and cancer. Understanding collagen IV PTMs is crucial for elucidating the molecular basis of these diseases and improving targeted treatments. By reviewing our knowledge of collagen IV biosynthesis, we illustrate how this evolutionarily conserved yet highly specialized molecular biosynthesis ensemble supports the diverse functions of collagen IV in health and disease.

IV型胶原是一种重要的、进化上保守的基底膜成分，是最广泛的翻译后修饰蛋白之一。尽管对纤维性胶原的生物合成进行了大量的研究，但我们对IV型胶原的生物合成，包括其翻译后修饰（PTMs）的了解仍然有限。大多数PTMs发生在细胞内，主要发生在内质网（ER）内。在这篇综述中，我们研究了内质网中协调IV型胶原生物合成的分子集合，强调了脯氨酸和赖氨酸羟化酶、糖基转移酶和分子伴侣之间的复杂相互作用。此外，我们还讨论了IV型胶原及其PTMs中的缺陷如何导致各种人类病理，包括Gould和Alport综合征、纤维化和癌症。了解胶原IV型PTMs对于阐明这些疾病的分子基础和改善靶向治疗至关重要。通过回顾我们对IV型胶原蛋白生物合成的了解，我们说明了这种进化上保守但高度特化的分子生物合成合体如何支持IV型胶原蛋白在健康和疾病中的多种功能。

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引用次数: 0

Paracrine regulations of IFN-γ secreting CD4+ T cells by lumican and biglycan are protective in allergic contact dermatitis lumican和biglycan对IFN-γ分泌CD4+ T细胞的旁分泌调节在过敏性接触性皮炎中具有保护作用

IF 4.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Matrix Biology

Pub Date : 2025-06-14 DOI: 10.1016/j.matbio.2025.06.002

George Maiti , Jihane Frikeche , Cynthia Loomis , Michael Cammer , Stephanie L Eichman , Shukti Chakravarti

Allergic contact dermatitis (ACD) is a delayed-type IV hypersensitivity response driven by innate and adaptive immune cells. While specific immune regulations of these cell types are amply elucidated, their regulations by extracellular matrix (ECM) components and T cell mediated adaptive immunity in ACD remains unclear. Lumican and biglycan are ECM proteoglycans abundant in the dermis and lymph node, known to regulate innate immune myeloid cells, but have not been investigated in lymphoid cell regulations in ACD. By immunohistology we localized lumican and biglycan in skin biopsies of psoriatic patients. Using wild type (WT), lumican and biglycan knockout mice, we investigated CD4⁺T cell infiltration, activation and proliferation in the skin and draining lymph node (dLN) of contact hypersensitivity (CHS)-challenged mice by immunohistochemistry and flow cytometry. We used the OT-II adoptive transfer model to test antigen specific CD4⁺T cell activation. We assessed interactions of the proteoglycans with LFA-1 on T cells by confocal microscopy. Compared to WTs, the knockouts showed severe ear inflammation, with increased CD4⁺T cells infiltration in the dermis. CHS-challenged knockout mice dLN showed increased T-bet, STAT1 and -STAT4 signaling, indicating enhanced Th1 commitment and proliferation. We found that WT lymph node fibroblastic reticular cells (FRCs) secrete lumican, biglycan and decorin, a related proteoglycan, while none are expressed by naive or activated T cells. Lumican and biglycan interact with LFA-1 on T cell surfaces, and in vitro all three proteoglycans suppress CD4⁺T cell activation. Secreted by dLN FRCs, lumican, biglycan, and possibly decorin interact with LFA-1 on CD4⁺T cells to restrict their activation and reduce dermatitis severity.

过敏性接触性皮炎（ACD）是一种由先天和适应性免疫细胞驱动的延迟型IV超敏反应。虽然这些细胞类型的特异性免疫调节已被充分阐明，但它们在ACD中由细胞外基质（ECM）成分和T细胞介导的适应性免疫的调节尚不清楚。Lumican和biglycan是真皮和淋巴结中丰富的ECM蛋白聚糖，已知可调节先天性免疫髓细胞，但尚未研究ACD中淋巴样细胞的调节。通过免疫组织学方法，我们在银屑病患者的皮肤活检中定位了lumican和biglycan。以野生型（WT）、lumican和biglycan敲除小鼠为实验对象，采用免疫组织化学和流式细胞术研究了CD4+T细胞在chs小鼠皮肤和引流淋巴结（dLN）中的浸润、活化和增殖情况。我们使用OT-II过继转移模型来检测抗原特异性CD4+T细胞活化。我们通过共聚焦显微镜评估了蛋白聚糖与LFA-1在T细胞上的相互作用。与WTs相比，敲除组表现出严重的耳部炎症，真皮中CD4+T细胞浸润增加。chs敲除小鼠dLN显示T-bet、STAT1和-STAT4信号增加，表明Th1承诺和增殖增强。我们发现WT淋巴结成纤维网状细胞（FRCs）分泌lumican， biglycan和decorin，一种相关的蛋白聚糖，而未被初始或活化的T细胞表达。Lumican和biglycan在T细胞表面与LFA-1相互作用，并且这三种蛋白多糖在体外都能抑制CD4+T细胞的激活。由dLN FRCs分泌的lumican、biglycan和可能的decorin与CD4+T细胞上的LFA-1相互作用，限制其激活，降低皮炎的严重程度。

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引用次数: 0