Department of Nephrology, University of Munich, Munich, Germany.
Kidney Int. 2010 Jul;78(1):29-37. doi: 10.1038/ki.2010.111. Epub 2010 Apr 28.
Inflammation is the immune system's response to infectious or noninfectious sources of danger. Danger recognition is facilitated by various innate immune receptor families including the Toll-like receptors (TLRs), which detect danger signals in extracellular and intracellular compartments. It is an evolving concept that renal damage triggers intrarenal inflammation by immune recognition of molecules that are being released by dying cells. Such danger-associated molecules act as immunostimulatory agonists to TLRs and other innate immune receptors and induce cytokine and chemokine secretion, leukocyte recruitment, and tissue remodeling. As a new entry to this concept, autophagy allows stressed cells to reduce intracellular microorganisms, protein aggregates, and cellular organelles by moving and subsequently digesting them in autophagolysosomes. Within the autophagolysosome, endogenous molecules and danger-associated molecules may be presented to TLRs or loaded onto the major histocompatibility complex and presented as autoantigens. Here we discuss the current evidence for the danger signaling concept in autoimmune kidney injury and propose that autophagy-related processing of self-proteins provides a source of immunostimulatory molecules and autoantigens. A better understanding of danger signaling should enable us to unravel yet unknown triggers for renal immunopathology and progressive kidney disease.
炎症是免疫系统对感染或非感染性危险源的反应。各种先天免疫受体家族（包括 Toll 样受体）促进了危险识别，这些受体在外周和细胞内环境中检测危险信号。一个不断发展的概念是，肾脏损伤通过对死亡细胞释放的分子的免疫识别，触发肾脏内炎症。这些危险相关分子作为免疫刺激激动剂作用于 TLR 和其他先天免疫受体，并诱导细胞因子和趋化因子的分泌、白细胞的募集和组织重塑。作为这一概念的新进展，自噬允许应激细胞通过移动并随后在自噬溶酶体中消化它们，从而减少细胞内微生物、蛋白质聚集体和细胞细胞器。在自噬溶酶体中，内源性分子和危险相关分子可以被呈递给 TLR 或加载到主要组织相容性复合物上，并作为自身抗原呈现。在这里，我们讨论了自身免疫性肾损伤中危险信号概念的现有证据，并提出自噬相关的自我蛋白加工为免疫刺激分子和自身抗原提供了来源。更好地理解危险信号应该使我们能够揭示肾脏免疫病理学和进行性肾病的未知触发因素。
