Lung-resident macrophages, which include alveolar macrophages and interstitial macrophages (IMs), exhibit a high degree of diversity, generally attributed to different activation states, and often complicated by the influx of monocytes into the pool of tissue-resident macrophages. To gain a deeper insight into the functional diversity of IMs, here we perform comprehensive transcriptional profiling of resident IMs and reveal ten distinct chemokine-expressing IM subsets at steady state and during inflammation. Similar IM subsets that exhibited coordinated chemokine signatures and differentially expressed genes were observed across various tissues and species, indicating conserved specialized functional roles. Other macrophage types shared specific IM chemokine profiles, while also presenting their own unique chemokine signatures. Depletion of CD206^hi IMs in Pf4^creR26^EYFP+DTR and Pf4^creR26^EYFPCx3cr1^DTR mice led to diminished inflammatory cell recruitment, reduced tertiary lymphoid structure formation and fewer germinal center B cells in models of allergen- and infection-driven inflammation. These observations highlight the specialized roles of IMs, defined by their coordinated chemokine production, in regulating immune cell influx and organizing tertiary lymphoid tissue architecture.

肺驻留巨噬细胞，包括肺泡巨噬细胞和间质巨噬细胞（IM），表现出高度的多样性，通常归因于不同的激活状态，并且通常因单核细胞流入组织驻留巨噬细胞库而变得复杂。为了更深入地了解 IM 的功能多样性，我们对常驻 IM 进行全面的转录分析，并揭示了稳定状态和炎症期间十种不同的表达趋化因子的 IM 子集。在不同组织和物种中观察到表现出协调趋化因子特征和差异表达基因的类似 IM 子集，表明保守的特殊功能作用。其他类型的巨噬细胞共享特定的 IM 趋化因子谱，同时也呈现出自己独特的趋化因子特征。在过敏原和感染驱动的炎症模型中，Pf4 ^cre R26 ^EYFP+DTR和Pf4 ^cre R26 ^EYFP Cx3cr1 ^DTR小鼠中CD206 ^hi IM的耗竭导致炎症细胞募集减少、三级淋巴结构形成减少以及生发中心 B 细胞减少。这些观察结果强调了 IM 在调节免疫细胞流入和组织三级淋巴组织结构中的特殊作用（由其协调趋化因子的产生定义）。