The actin-regulatory protein Hem-1 is essential for alveolar macrophage development.
The actin-regulatory protein Hem-1 is essential for alveolar macrophage development.
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DOI：
10.1084/jem.20200472
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发表时间：
2021-04-05
期刊：
影响因子：
--
通讯作者：
Iritani BM
中科院分区：
文献类型：
--
作者：
Suwankitwat N;Libby S;Liggitt HD;Avalos A;Ruddell A;Rosch JW;Park H;Iritani BM
肌动蛋白调节蛋白Hem-1的突变导致人类原发性免疫缺陷病。Suwankitwat等人使用小鼠模型表明，骨髓特异性Hem-1对于肺泡巨噬细胞的发育以及针对甲型流感病毒和肺炎链球菌的保护是必需的。造血蛋白-1（Hemopoieticprotein-1，Hem-1）是一种造血细胞特异性肌动蛋白调节蛋白。最近发现编码Hem-1的NCKAP 1 L基因中的功能丧失（LOF）变体导致人类原发性免疫缺陷病（PID），其特征在于复发性呼吸道感染、哮喘和高死亡率。然而，Hem-1变体如何导致PID的机制尚不清楚。在这项研究中，我们产生了组成型和骨髓细胞特异性Nckap 1 l-KO小鼠，以剖析Hem-1在肺免疫中的重要性。我们发现，Hem-1缺陷小鼠积累过多的表面活性剂和细胞碎片在气道（肺泡蛋白沉积症）由于受损的发展肺泡巨噬细胞（AM）和AM分化因子Pparg的表达减少。残留的Hem-1缺陷型AM转变为促炎表型，Hem-1缺陷型中性粒细胞和单核细胞不能正常迁移。骨髓细胞特异性Hem-1缺陷小鼠在甲型流感病毒或肺炎链球菌攻击后表现出发病率增加。这些结果为Hem-1中的LOF变体如何导致复发性呼吸道疾病提供了潜在的机制。
Mutations in the actin-regulatory protein Hem-1 result in primary immunodeficiency disease in humans. Using murine models, Suwankitwat et al. show that myeloid-specific Hem-1 is essential for the development of alveolar macrophages and protection against influenza A virus and Streptococcus pneumoniae. Hematopoietic protein-1 (Hem-1) is a hematopoietic cell–specific actin-regulatory protein. Loss-of-function (LOF) variants in the NCKAP1L gene encoding Hem-1 have recently been found to result in primary immunodeficiency disease (PID) in humans, characterized by recurring respiratory infections, asthma, and high mortality. However, the mechanisms of how Hem-1 variants result in PID are not known. In this study, we generated constitutive and myeloid cell–specific Nckap1l-KO mice to dissect the importance of Hem-1 in lung immunity. We found that Hem-1–deficient mice accumulated excessive surfactant and cell debris in airways (pulmonary alveolar proteinosis) due to impaired development of alveolar macrophages (AMs) and reduced expression of the AM differentiation factor Pparg. Residual Hem-1–deficient AMs shifted to a proinflammatory phenotype, and Hem-1–deficient neutrophils and monocytes failed to migrate normally. Myeloid cell–specific Hem-1–deficient mice exhibited increased morbidity following influenza A virus or Streptococcus pneumoniae challenge. These results provide potential mechanisms for how LOF variants in Hem-1 result in recurring respiratory diseases.
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影响因子：
6.5
作者：
Baker, Anna D.;Malur, Anagha;Thomassen, Mary Jane
通讯作者：
Thomassen, Mary Jane
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
肺泡巨噬细胞从胎儿单核细胞中发展，这些单核细胞在生命的第一周通过GM-CSF分化为长寿命细胞。
DOI：
10.1084/jem.20131199
发表时间：
2013-09-23
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guilliams M;De Kleer I;Henri S;Post S;Vanhoutte L;De Prijck S;Deswarte K;Malissen B;Hammad H;Lambrecht BN
通讯作者：
Lambrecht BN
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
DOI：
10.1084/jem.20130028
发表时间：
2013-10-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Nakamura A;Ebina-Shibuya R;Itoh-Nakadai A;Muto A;Shima H;Saigusa D;Aoki J;Ebina M;Nukiwa T;Igarashi K
通讯作者：
Igarashi K