比利时VIB-UGent炎症研究中心Bart N. Lambrecht小组取得一项新突破。他们的研究显示，先天2型淋巴细胞触发肺泡巨噬细胞的炎症开关。该研究于2025年12月11日发表于国际一流学术期刊《免疫学》杂志上。

通过一个小鼠模型，研究团队发现trAM在2型免疫过程中具有促炎作用。暴露于过敏原后，白细胞介素-33激活的先天2型淋巴细胞（ILC2s）产生白细胞介素-13，其通过诱导转录因子干扰素调节因子4 （IRF4）重编程trAMs。IRF4抑制转录因子过氧化物酶体增殖体激活受体γ (PPARγ)的表达，并拆除PPARγ依赖的稳态调节，该调节定义了trAM的身份，同时启动转录程序驱动趋化因子的产生和细胞凋亡。这导致粒细胞、ILC2s和调节性T细胞的募集，以及肺泡生态位中多核巨细胞的形成。然后，PPARγ-to-IRF4开关将trAMs重新配置为促炎效应物，促进过敏原诱导的肺部病理。

研究人员表示，组织驻留肺泡巨噬细胞（trAMs）通过抑制炎症保护气体交换。与募集的肺泡巨噬细胞（recAMs）相比，trAMs被认为具有更强的免疫调节能力和抗炎症重编程能力。

附：英文原文

Title: Innate type 2 lymphocytes trigger an inflammatory switch in alveolar macrophages

Author: Stijn Verwaerde, Jean-Franois Hastir, Sjoerd T.T. Schetters, Ursula Smole, Leen Seys, Antonio P. Baptista, Kieran English, Martijn J. Schuijs, Helena Aegerter, Karel F.A. Van Damme, Aimée Bugler-Lamb, Nikita Gerebtsov, Wendy Toussaint, Tatsuma Ban, Tomohiko Tamura, Florent Ginhoux, Zhaoyuan Liu, Wouter Saelens, Hamida Hammad, Martin Guilliams, Bart N. Lambrecht

Issue&Volume: 2025-12-11

Abstract: Tissue-resident alveolar macrophages (trAMs) safeguard gas exchange by restraining inflammation. Compared with recruited alveolar macrophages (recAMs), trAMs are considered more immunoregulatory and resilient to inflammatory reprogramming. Using a mouse model enabling selective trAM depletion and replacement, we uncovered a pro-inflammatory role for trAMs during type 2 immunity. Upon allergen exposure, interleukin-33-activated innate type 2 lymphoid cells (ILC2s) produced interleukin-13, which reprogrammed trAMs through induction of the transcription factor interferon regulatory factor 4 (IRF4). IRF4 suppressed the expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and dismantled the PPARγ-dependent homeostatic regulon that defines trAM identity, while initiating a transcriptional program driving chemokine production and cell fusion. This resulted in the recruitment of granulocytes, ILC2s, and regulatory T cells, as well as the formation of multinucleated giant cells in the alveolar niche. Thus, a PPARγ-to-IRF4 switch reconfigures trAMs into pro-inflammatory effectors, promoting allergen-induced lung pathology.

DOI: 10.1016/j.immuni.2025.11.015

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00517-5