Rate of replenishment and microenvironment contribute to the sexually dimorphic phenotype and function of peritoneal macrophages.
Rate of replenishment and microenvironment contribute to the sexually dimorphic phenotype and function of peritoneal macrophages.
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DOI：
10.1126/sciimmunol.abc4466
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发表时间：
2020-06-19
影响因子：
24.8
通讯作者：
Jenkins SJ
中科院分区：
文献类型：
--
作者：
Bain CC;Gibson DA;Steers NJ;Boufea K;Louwe PA;Doherty C;González-Huici V;Gentek R;Magalhaes-Pinto M;Shaw T;Bajénoff M;Bénézech C;Walmsley SR;Dockrell DH;Saunders PTK;Batada NN;Jenkins SJ
巨噬细胞存在于体腔中，维持浆液稳态并提供免疫监视。腹膜巨噬细胞与腹膜炎、子宫内膜异位症和转移性癌等疾病的病因有关，因此了解控制其行为的因素至关重要。结合命运图谱技术，我们研究了性别和年龄对小鼠腹膜巨噬细胞分化、周转和功能的影响。我们证明，来自骨髓的腹膜巨噬细胞的两性二态补充，在雄性中很高，在雌性中很低，是由性成熟时产生的局部微环境变化驱动的。群体和单细胞RNAseq揭示了男性和女性腹膜巨噬细胞之间基因表达的显著二态性，这在一定程度上可以解释为这些群体组成的差异。通过估计不同亚群在腔内的停留时间，并评估随年龄增长和单核减少性Ccr2 -/-小鼠二态性的发展，我们证明了腹膜巨噬细胞的关键性别依赖性特征是骨髓补充率差异的功能，而其他特征则依赖于局部微环境信号。重要的是，我们证明了腹膜巨噬细胞的二态转换有助于两性之间对肺炎球菌性腹膜炎的保护能力的差异。这些数据强调了在对炎症和传染病的易感性方面同时考虑性别和年龄的重要性。
Macrophages reside in the body cavities where they maintain serosal homeostasis and provide immune surveillance. Peritoneal macrophages are implicated in the etiology of pathologies including peritonitis, endometriosis and metastatic cancer thus understanding the factors that govern their behavior is vital. Using a combination of fate mapping techniques, we have investigated the impact of sex and age on murine peritoneal macrophage differentiation, turnover and function. We demonstrate that the sexually dimorphic replenishment of peritoneal macrophages from the bone marrow, which is high in males and very low in females, is driven by changes in the local microenvironment that arise upon sexual maturation. Population and single cell RNAseq revealed striking dimorphisms in gene expression between male and female peritoneal macrophages that was in part explained by differences in composition of these populations. By estimating the time of residency of different subsets within the cavity and assessing development of dimorphisms with age and in monocytopenic Ccr2 -/- mice, we demonstrate that key sex-dependent features of peritoneal macrophages are a function of the differential rate of replenishment from the bone marrow while others are reliant on local microenvironment signals. Importantly, we demonstrate that the dimorphic turnover of peritoneal macrophages contributes to differences in the ability to protect against pneumococcal peritonitis between the sexes. These data highlight the importance of considering both sex and age in susceptibility to inflammatory and infectious diseases.
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影响因子：
20.3
作者：
Gautier, Emmanuel L.;Ivanov, Stoyan;Randolph, Gwendalyn J.
通讯作者：
Randolph, Gwendalyn J.
DOI：
10.1084/jem.20062648
发表时间：
2007-07-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Caton ML;Smith-Raska MR;Reizis B
通讯作者：
Reizis B
影响因子：
30.5
作者：
Dick, Sarah A.;Macklin, Jillian A.;Epelman, Slava
通讯作者：
Epelman, Slava
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
2.2
作者：
Burnett, SH;Beus, BJ;Cohen, DA
通讯作者：
Cohen, DA