First-Breath-Induced Type 2 Pathways Shape the Lung Immune Environment.
First-Breath-Induced Type 2 Pathways Shape the Lung Immune Environment.
复制标题
第一次呼吸诱导的 2 型通路塑造肺部免疫环境。
DOI：
10.1016/j.celrep.2017.01.071
复制
发表时间：
2017-02-21
期刊：
影响因子：
8.8
通讯作者：
Knapp S
中科院分区：
文献类型：
--
作者：
Saluzzo S;Gorki AD;Rana BMJ;Martins R;Scanlon S;Starkl P;Lakovits K;Hladik A;Korosec A;Sharif O;Warszawska JM;Jolin H;Mesteri I;McKenzie ANJ;Knapp S
从出生起，肺部就暴露在外部环境中，因此拥有复杂的免疫环境来保护该器官免受损伤和感染。我们研究了上皮源性警报蛋白白细胞介素 33 (IL-33) 在新生小鼠中的稳态作用，发现 IL-33 从生命第一天起立即上调，紧随其后的是一波产生 IL-13 的 2 型先天淋巴细胞 (ILC2)，这与肺泡巨噬细胞 (AM) 的出现及其早期极化为 IL-13 依赖性抗炎 M2 相一致。表型。 ILC2 通过极化组织驻留 AM 来促进肺稳态稳态，并在移植的巨噬细胞祖细胞中诱导 M2 表型。 ILC2 在成年期间继续维持 M2 AM 表型，但代价是小鼠对肺炎链球菌感染的反应延迟。这些数据强调了 ILC2 在设定肺部激活阈值中的稳态作用，并强调了它们在抗菌防御中的意义。第一次呼吸触发新生小鼠肺部 AEC2 诱导 IL-33 IL-33 促进表达 ST2 的 ILC2 的围产期扩张和激活 ILC2 衍生的 IL-13 将新生儿的 AM 极化为 M2 表型 这种稳态 2 型途径延迟抗菌效应反应 出生后肺部免疫环境在很大程度上尚未被探索。萨卢佐等人。发现出生与小鼠中 IL-33/ILC2/IL-13 驱动的免疫反应的诱导有关。这种 2 型反应在整个生命过程中都会保留，并以 M2 表型维持肺泡巨噬细胞，但代价是对细菌感染的反应延迟。
From birth onward, the lungs are exposed to the external environment and therefore harbor a complex immunological milieu to protect this organ from damage and infection. We investigated the homeostatic role of the epithelium-derived alarmin interleukin-33 (IL-33) in newborn mice and discovered the immediate upregulation of IL-33 from the first day of life, closely followed by a wave of IL-13-producing type 2 innate lymphoid cells (ILC2s), which coincided with the appearance of alveolar macrophages (AMs) and their early polarization to an IL-13-dependent anti-inflammatory M2 phenotype. ILC2s contributed to lung quiescence in homeostasis by polarizing tissue resident AMs and induced an M2 phenotype in transplanted macrophage progenitors. ILC2s continued to maintain the M2 AM phenotype during adult life at the cost of a delayed response to Streptococcus pneumoniae infection in mice. These data highlight the homeostatic role of ILC2s in setting the activation threshold in the lung and underline their implications in anti-bacterial defenses. The first breath triggers IL-33 induction by AEC2 in lungs of newborn mice IL-33 promotes the perinatal expansion and activation of ST2-expressing ILC2s ILC2-derived IL-13 polarizes newborn’s AMs into an M2 phenotype This homeostatic type 2 pathway delays antibacterial effector responses The postnatal lung immune environment is largely unexplored. Saluzzo et al. find that birth is associated with the induction of an IL-33/ILC2/IL-13-driven immune response in mice. This type 2 response is preserved throughout life and maintains alveolar macrophages in an M2 phenotype at the expense of a delayed response to bacterial infections.