Emerging Roles of Innate Immune Signaling and Toll-Like Receptors in Fibrosis and Systemic Sclerosis
Emerging Roles of Innate Immune Signaling and Toll-Like Receptors in Fibrosis and Systemic Sclerosis
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DOI：
10.1007/s11926-014-0474-z
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发表时间：
2015-01-01
影响因子：
5
通讯作者：
Varga, John
中科院分区：
文献类型：
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作者：
Bhattacharyya, Swati;Varga, John
病理性纤维化是系统性硬化症（SSc）以及许多更常见病症的显著标志。纤维化是一种复杂的动态过程，与免疫失调、血管病变和不受控制的细胞外基质产生相关，导致皮肤和内脏器官中的顽固性瘢痕形成。遗传易感个体的持续或复发性化学、感染性、机械或自身免疫损伤导致持续的成纤维细胞活化。通过Toll样受体（TLR）的先天免疫信号传导越来越被认为是驱动SSc持续纤维化反应的关键因素。特别地，TLR 4及其内源性配体的表达在来自SSc患者的病变组织中升高。配体诱导的TLR 4活化对纤维化基因表达和肌成纤维细胞分化具有强刺激作用。此外，TLR 4似乎使成纤维细胞对转化生长因子-β的促纤维化刺激作用敏感。这篇综述强调了最近的进展和新出现的范例，了解调节，复杂的功能作用，并在SSc发病机制的TLRs的治疗潜力。
Pathological fibrosis is a distinguishing hallmark of systemic sclerosis (SSc) as well as a number of more common conditions. Fibrosis is a complex and dynamic process associated with immune dysregulation, vasculopathy, and uncontrolled extracellular matrix production leading to intractable scar formation in the skin and internal organs. Persistent or recurrent chemical, infectious, mechanical, or autoimmune injury in genetically predisposed individuals causes sustained fibroblasts activation. Innate immune signaling via toll-like receptors (TLRs) is increasingly recognized as a key player driving the persistent fibrotic response in SSc. In particular, expression of TLR4 as well as its endogenous ligands are elevated in lesional tissue from patients with SSc. Ligand-induced TLR4 activation elicits potent stimulatory effects on fibrotic gene expression and myofibroblast differentiation. Furthermore, TLR4 appears to sensitize fibroblasts to the profibrotic stimulatory effect of transforming growth factor-beta. This review highlights recent advances and emerging paradigms for understanding the regulation, complex functional roles, and therapeutic potential of TLRs in SSc pathogenesis.