Department of Biosciences and Medical Biology, Paris Lodron University of Salzburg, Salzburg, Austria.
Center for Tumor Biology and Immunology, Paris Lodron University of Salzburg, Salzburg, Austria.
Front Immunol. 2024 Jun 12;15:1393819. doi: 10.3389/fimmu.2024.1393819. eCollection 2024.
INTRODUCTION & OBJECTIVE: Allergic sensitization is an essential step in the development of allergic airway inflammation to birch pollen (BP); however, this process remains to be fully elucidated. Recent scientific advances have highlighted the importance of the allergen context. In this regard, microbial patterns (PAMPs) present on BP have attracted increasing interest. As these PAMPs are recognized by specialized pattern recognition receptors (PRRs), this study aims at investigating the roles of intracellular PRRs and the inflammasome regulator NLRP3.
We established a physiologically relevant intranasal and adjuvant-free sensitization procedure to study BP-induced systemic and local lung inflammation.
Strikingly, BP-sensitized -deficient mice showed significantly lower IgE levels, Th2-associated cytokines, cell infiltration into the lung, mucin production and epithelial thickening than their wild-type counterparts, which appears to be independent of inflammasome formation. Intriguingly, bone-marrow chimera revealed that expression of NLRP3 in the hematopoietic system is required to trigger an allergic response.
Overall, this study identifies NLRP3 as an important driver of BP-induced allergic immune responses.
过敏致敏是桦树花粉(BP)引起过敏性气道炎症的必要步骤,但这一过程仍有待充分阐明。最近的科学进展强调了过敏原背景的重要性。在这方面,BP 上存在的微生物模式(PAMPs)引起了越来越多的关注。由于这些 PAMPs 被专门的模式识别受体(PRRs)识别,因此本研究旨在研究细胞内 PRRs 和炎性体调节剂 NLRP3 的作用。
我们建立了一种生理相关的鼻内和无佐剂致敏程序,以研究 BP 诱导的全身和肺部局部炎症。
令人惊讶的是,BP 致敏的 -缺陷小鼠的 IgE 水平、Th2 相关细胞因子、细胞浸润到肺部、粘蛋白产生和上皮增厚均显著低于野生型小鼠,这似乎与炎性体的形成无关。有趣的是,骨髓嵌合体显示 NLRP3 在造血系统中的表达是引发过敏反应所必需的。
总的来说,这项研究确定 NLRP3 是 BP 诱导的过敏免疫反应的重要驱动因素。