C-Type Lectin-Like Receptors As Emerging Orchestrators of Sterile Inflammation Represent Potential Therapeutic Targets.
C-Type Lectin-Like Receptors As Emerging Orchestrators of Sterile Inflammation Represent Potential Therapeutic Targets.
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DOI：
10.3389/fimmu.2018.00227
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发表时间：
2018
影响因子：
7.3
通讯作者：
Chiffoleau E
中科院分区：
文献类型：
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作者：
Chiffoleau E
在过去的十年中，主要由骨髓细胞表达的C型凝集素样受体（CTLR）因其在先天性和适应性免疫的微调中的作用而受到越来越多的关注。CTLR不仅识别病原体来源的配体以防止感染，还识别内源性配体（例如自身碳水化合物、蛋白质或脂质）以控制体内平衡和组织损伤。有趣的是，CTLR通过其碳水化合物识别结构域充当抗原摄取受体，用于内化并随后呈递给T细胞。此外，CTLR通过复杂的细胞内网络发出信号，导致分泌一组特定的细胞因子，其根据配体和模式识别受体的共接合而不同地极化下游效应T细胞应答。因此，通过协调炎症和消退途径之间的平衡，CTLR现在被认为是无菌炎症的驱动因素，其失调导致各种病理学的发展，如自身免疫性疾病、过敏或癌症。例如，巨噬细胞诱导的C型凝集素（MINCLE）通过感知细胞损伤期间释放的糖脂，促进皮肤过敏和实验性自身免疫性葡萄膜视网膜炎的发病机制。此外，最近的研究表明，肿瘤利用CTLR的树突状细胞相关C型凝集素-1（DECTIN-1）和MINCLE的生理过程来局部抑制骨髓细胞活化并促进免疫逃避。因此，我们的目的是概述目前的知识的关键作用，CTLR在无菌性炎症，特别注意的“Dectin-1”和“Dectin-2”的家庭。此外，我们将讨论这些受体作为治疗各种急性和慢性疾病的有前途的治疗靶点的潜力。
Over the last decade, C-type lectin-like receptors (CTLRs), expressed mostly by myeloid cells, have gained increasing attention for their role in the fine tuning of both innate and adaptive immunity. Not only CTLRs recognize pathogen-derived ligands to protect against infection but also endogenous ligands such as self-carbohydrates, proteins, or lipids to control homeostasis and tissue injury. Interestingly, CTLRs act as antigen-uptake receptors via their carbohydrate-recognition domain for internalization and subsequent presentation to T-cells. Furthermore, CTLRs signal through a complex intracellular network leading to the secretion of a particular set of cytokines that differently polarizes downstream effector T-cell responses according to the ligand and pattern recognition receptor co-engagement. Thus, by orchestrating the balance between inflammatory and resolution pathways, CTLRs are now considered as driving players of sterile inflammation whose dysregulation leads to the development of various pathologies such as autoimmune diseases, allergy, or cancer. For examples, the macrophage-inducible C-type lectin (MINCLE), by sensing glycolipids released during cell-damage, promotes skin allergy and the pathogenesis of experimental autoimmune uveoretinitis. Besides, recent studies described that tumors use physiological process of the CTLRs’ dendritic cell-associated C-type lectin-1 (DECTIN-1) and MINCLE to locally suppress myeloid cell activation and promote immune evasion. Therefore, we aim here to overview the current knowledge of the pivotal role of CTLRs in sterile inflammation with special attention given to the “Dectin-1” and “Dectin-2” families. Moreover, we will discuss the potential of these receptors as promising therapeutic targets to treat a wide range of acute and chronic diseases.