Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Front Immunol. 2023 Mar 23;14:1161606. doi: 10.3389/fimmu.2023.1161606. eCollection 2023.
Endometriosis is closely associated with ectopic focal inflammation and immunosuppressive microenvironment. Multiple types of pattern recognition receptors (PRRs) are present in the innate immune system, which are able to detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) in both intracellular and external environments. However, the exact role of PRRs in endometriosis and the underlying molecular mechanism are unclear. PRRs are necessary for the innate immune system to identify and destroy invasive foreign infectious agents. Mammals mainly have two types of microbial recognition systems. The first one consists of the membrane-bound receptors, such as toll-like receptors (TLRs), which recognize extracellular microorganisms and activate intracellular signals to stimulate immune responses. The second one consists of the intracellular PRRs, including nod-like receptors (NLRs) and antiviral proteins retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA-5) with helix enzyme domain. In this review, we mainly focus on the key role of PRRs in the pathological processes associated with endometriosis. PRRs recognize PAMPs and can distinguish pathogenic microorganisms from self, triggering receptor ligand reaction followed by the stimulation of host immune response. Activated immune response promotes the transmission of microbial infection signals to the cells. As endometriosis is characterized by dysregulated inflammation and immune response, PRRs may potentially be involved in the activation of endometriosis-associated inflammation and immune disorders. Toll-like receptor 2 (TLR2), toll-like receptor 3 (TLR3), toll-like receptor 4 (TLR4), nod-like receptor family caspase activation and recruitment domain (CARD) domain containing 5 (NLRC5), nod-like receptor family pyrin domain containing 3 (NLRP3), and c-type lectin receptors (CLRs) play essential roles in endometriosis development by regulating immune and inflammatory responses. Absent in melanoma 2 (AIM2)-like receptors (ALRs) and retinoic acid-inducible gene I-like receptors (RLRs) may be involved in the activation of endometriosis-associated immune and inflammation disorders. PRRs, especially TLRs, may serve as potential therapeutic targets for alleviating pain in endometriosis patients. PRRs and their ligands interact with the innate immune system to enhance inflammation in the stromal cells during endometriosis. Thus, targeting PRRs and their new synthetic ligands may provide new therapeutic options for treating endometriosis.
子宫内膜异位症与异位局灶性炎症和免疫抑制微环境密切相关。固有免疫系统中存在多种模式识别受体 (PRR)，能够在细胞内和细胞外环境中检测病原体相关的分子模式 (PAMP) 和危险相关的分子模式 (DAMP)。然而，PRR 在子宫内膜异位症中的确切作用及其潜在的分子机制尚不清楚。PRR 是固有免疫系统识别和破坏入侵的外来传染性病原体所必需的。哺乳动物主要有两种微生物识别系统。第一种是由膜结合受体组成，例如 Toll 样受体 (TLR)，它识别细胞外微生物并激活细胞内信号以刺激免疫反应。第二种是由细胞内 PRR 组成，包括核苷酸结合寡聚化结构域样受体 (NLR) 和抗病毒蛋白视黄酸诱导基因 I (RIG-I) 和黑色素瘤分化相关基因 5 (MDA-5) 与螺旋酶结构域。在这篇综述中，我们主要关注 PRR 在与子宫内膜异位症相关的病理过程中的关键作用。PRR 识别 PAMP，并能区分致病微生物和自身，触发受体配体反应，继而刺激宿主免疫反应。激活的免疫反应促进微生物感染信号向细胞的传递。由于子宫内膜异位症的特点是炎症和免疫反应失调，PRR 可能潜在地参与激活与子宫内膜异位症相关的炎症和免疫紊乱。Toll 样受体 2 (TLR2)、Toll 样受体 3 (TLR3)、Toll 样受体 4 (TLR4)、核苷酸结合寡聚化结构域样受体家族含 caspase 激活和募集结构域 (CARD) 域 5 (NLRC5)、核苷酸结合寡聚化结构域样受体家族含 pyrin 结构域 3 (NLRP3) 和 C 型凝集素受体 (CLR) 通过调节免疫和炎症反应在子宫内膜异位症的发展中发挥重要作用。黑色素瘤缺失 2 (AIM2) 样受体 (ALR) 和视黄酸诱导基因 I 样受体 (RLR) 可能参与激活与子宫内膜异位症相关的免疫和炎症紊乱。PRR，尤其是 TLR，可能成为缓解子宫内膜异位症患者疼痛的潜在治疗靶点。PRR 及其配体与固有免疫系统相互作用，在子宫内膜异位症期间增强基质细胞中的炎症反应。因此，靶向 PRR 及其新合成配体可能为治疗子宫内膜异位症提供新的治疗选择。
