TL1A的形态学转变与鼻窦炎及过敏性鼻炎中的炎症异质性：一篇假说驱动的综述。

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中文摘要

背景： 过敏性鼻炎（AR）和慢性鼻窦炎（CRS）是异质性的上气道炎症性疾病，其中2型炎症常见，但并不能完全解释所有临床内型或治疗反应。本综述综合了关于肿瘤坏死因子样配体1A（TL1A）的证据，并探讨其膜结合型（mTL1A）和可溶型（sTL1A）形式是否可能连接上皮损伤、巨噬细胞活化及混合性炎症网络。方法：来自肠道和下气道模型的证据支持TL1A/DR3信号在多种免疫背景中的作用，而鼻窦研究仅提供有限的、细胞特异性的证据，尚未确立局部TL1A丰度、脱落动力学或完整的以巨噬细胞为中心的反馈环路。结果：因此，我们提出一个可检验的模型，其中mTL1A可能支持接触依赖性信号传导，而上皮应激和蛋白酶介导的脱落可能产生具有更广泛旁分泌活性的可溶性TL1A。在此框架中，TL1A可能与IL-33、TSLP和IL-25协同作用，并可能激活涉及CXCL8/IL-8和IL-1beta的巨噬细胞依赖性级联反应。由于中性粒细胞通常被认为是TL1A/DR3信号的间接靶标，此类级联反应可能促成混合性或治疗难治性炎症，但这并不意味着TL1A单独即足以致病。结论：该模型为整合内型异质性以及识别可检验的生物标志物和治疗假说提供了概念框架，但仍需在人鼻窦组织、鼻灌洗液及相关实验模型中进行直接验证。

英文摘要

Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are heterogeneous upper-airway inflammatory disorders in which type 2 inflammation is common but does not fully explain all clinical endotypes or treatment responses. This review synthesizes evidence on tumor necrosis factor-like ligand 1A (TL1A) and considers whether its membrane-bound (mTL1A) and soluble (sTL1A) forms could connect epithelial injury, macrophage activation, and mixed inflammatory networks. Evidence from intestinal and lower-airway models supports TL1A/DR3 signaling in several immune contexts, while sinonasal studies provide only limited, cell-specific evidence and do not yet establish local TL1A abundance, shedding dynamics, or a complete macrophage-centered feedback loop. We therefore propose a testable model in which mTL1A may support contact-dependent signaling, whereas epithelial stress and protease-mediated shedding may generate soluble TL1A with broader paracrine activity. In this framework, TL1A could cooperate with IL-33, TSLP, and IL-25 and might activate macrophage-dependent relays involving CXCL8/IL-8 and IL-1beta. Because neutrophils are generally considered indirect targets of TL1A/DR3 signaling, such relays could contribute to mixed or treatment-refractory inflammation without implying that TL1A alone is sufficient. The model provides a conceptual framework for integrating endotypic heterogeneity and identifying testable biomarkers and therapeutic hypotheses, but direct validation in human sinonasal tissue, nasal lavage fluid, and relevant experimental models remains necessary.