Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared signaling pathways, and transcriptional programs. However, recent discoveries have revealed context-specific functional differences. Here, we provide a comprehensive review of type I and type III IFN activities, highlighting shared and distinct features from molecular mechanisms through physiological responses. Beyond discussing canonical antiviral functions, we consider the adaptive immune priming, anti-tumor, and autoimmune functions of IFNs. We discuss a model wherein type III IFNs serve as a front-line defense that controls infection at epithelial barriers while minimizing damaging inflammatory responses, reserving the more potent type I IFN response for when local responses are insufficient. In this context, we discuss current therapeutic applications targeting these cytokine pathways and highlight gaps in understanding of the biology of type I and type III IFNs in health and disease.

I 型干扰素 (IFN)（IFN-α、IFN-β）和 III 型干扰素 (IFN-λ) 具有许多共同特性，包括病毒感染诱导、共享信号通路激活和转录程序。然而，最近的发现揭示了特定环境的功能差异。在这里，我们对 I 型和 III 型 IFN 活性进行了全面综述，强调了从分子机制到生理反应的共同和独特特征。除了讨论典型的抗病毒功能外，我们还考虑了 IFN 的适应性免疫启动、抗肿瘤和自身免疫功能。我们讨论了一个模型，其中 III 型干扰素作为前线防御，控制上皮屏障的感染，同时最大限度地减少破坏性炎症反应，在局部反应不足时保留更有效的 I 型干扰素反应。在此背景下，我们讨论了当前针对这些细胞因子途径的治疗应用，并强调了对 I 型和 III 型 IFN 在健康和疾病中的生物学理解方面的差距。