In this review we highlight emerging immune regulatory functions of lumican, keratocan, fibromodulin, biglycan and decorin, which are members of the small leucine-rich proteoglycans (SLRP) of the extracellular matrix (ECM). These SLRPs have been studied extensively as collagen-fibril regulatory structural components of the skin, cornea, bone and cartilage in homeostasis. However, SLRPs released from a remodeling ECM, or synthesized by activated fibroblasts and immune cells contribute to an ECM-free pool in tissues and circulation, that may have a significant, but poorly understood foot print in inflammation and disease. Their molecular interactions and the signaling networks they influence also require investigations. Here we present studies on the leucine-rich repeat (LRR) motifs of SLRP core proteins, their evolutionary and functional relationships with other LRR pathogen recognition receptors, such as the toll-like receptors (TLRs) to bring some molecular clarity in the immune regulatory functions of SLRPs. We discuss molecular interactions of fragments and intact SLRPs, and how some of these interactions are likely modulated by glycosaminoglycan side chains. We integrate findings on molecular interactions of these SLRPs together with what is known about their presence in circulation and lymph nodes (LN), which are important sites of immune cell regulation. Recent bulk and single cell RNA sequencing studies have identified subsets of stromal reticular cells that express these SLRPs within LNs. An understanding of the cellular source, molecular interactions and signaling consequences will lead to a fundamental understanding of how SLRPs modulate immune responses, and to therapeutic tools based on these SLRPs in the future.

在这篇综述中，我们重点介绍了 lumican、keratocan、纤维调节蛋白、双糖链蛋白聚糖和核心蛋白聚糖的新兴免疫调节功能，它们是细胞外基质 (ECM) 的富含亮氨酸的小蛋白聚糖 (SLRP) 的成员。这些 SLRP 作为皮肤、角膜、骨骼和软骨稳态中的胶原纤维调节结构成分已被广泛研究。然而，重塑 ECM 释放的 SLRP 或由活化的成纤维细胞和免疫细胞合成的 SLRP 有助于在组织和循环中形成无 ECM 池，这可能在炎症和疾病中具有显着但尚不清楚的足迹。它们的分子相互作用和它们影响的信号网络也需要研究。在这里，我们介绍了 SLRP 核心蛋白的富含亮氨酸重复 (LRR) 基序、它们与其他 LRR 病原体识别受体（例如 Toll 样受体 (TLR)）的进化和功能关系的研究，以在免疫调节中带来一些分子清晰度SLRP 的功能。我们讨论了片段和完整 SLRP 的分子相互作用，以及其中一些相互作用如何可能受到糖胺聚糖侧链的调节。我们将这些 SLRP 分子相互作用的发现与它们在循环和淋巴结 (LN) 中存在的已知信息结合起来，这些是免疫细胞调节的重要部位。最近的大量和单细胞 RNA 测序研究已经确定了 LN 内表达这些 SLRP 的基质网状细胞亚群。对细胞来源、分子相互作用和信号转导结果的了解将使人们对 SLRP 如何调节免疫反应以及未来基于这些 SLRP 的治疗工具有一个基本的了解。