Inflammation is a fundamental biological process mediating host defense and wound healing during infections and tissue injury. Perpetuated and excessive inflammation may cause autoinflammation, autoimmunity, degenerative disorders, allergies, and malignancies. Multimodal signaling by tumor necrosis factor receptor 1 (TNFR1) plays a crucial role in determining the transition between inflammation, cell survival, and programmed cell death. Targeting TNF signaling has been proven as an effective therapeutic in several immune-related disorders. Mouse studies have provided critical mechanistic insights into TNFR1 signaling and its potential role in a broad spectrum of diseases. The characterization of patients with monogenic primary immunodeficiencies (PIDs) has highlighted the importance of TNFR1 signaling in human disease. In particular, patients with PIDs have revealed paradoxical connections between immunodeficiency, chronic inflammation, and dysregulated cell death. Importantly, studies on PIDs may help to predict beneficial effects and side-effects of therapeutic targeting of TNFR1 signaling.

中文翻译：

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人类慢性炎症中细胞死亡的失调。

炎症是在感染和组织损伤期间介导宿主防御和伤口愈合的基本生物学过程。持续和过度的炎症可能导致自身炎症、自身免疫、退行性疾病、过敏和恶性肿瘤。肿瘤坏死因子受体 1 (TNFR1) 的多模式信号传导在确定炎症、细胞存活和程序性细胞死亡之间的转换中起着至关重要的作用。靶向 TNF 信号传导已被证明是几种免疫相关疾病的有效治疗方法。小鼠研究为 TNFR1 信号传导及其在广泛疾病中的潜在作用提供了重要的机制见解。单基因原发性免疫缺陷 (PID) 患者的特征突出了 TNFR1 信号传导在人类疾病中的重要性。尤其是，PIDs 患者揭示了免疫缺陷、慢性炎症和失调的细胞死亡之间的矛盾联系。重要的是，对 PID 的研究可能有助于预测 TNFR1 信号传导靶向治疗的有益效果和副作用。