Interleukin 7 receptor is required for myeloid cell homeostasis and reconstitution by hematopoietic stem cells.
Interleukin 7 receptor is required for myeloid cell homeostasis and reconstitution by hematopoietic stem cells.
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DOI：
10.1016/j.exphem.2020.09.001
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发表时间：
2020-10
影响因子：
2.6
通讯作者：
Forsberg EC
中科院分区：
文献类型：
--
作者：
Cool T;Worthington A;Poscablo D;Hussaini A;Forsberg EC
呼吸系统疾病是世界范围内的主要死亡原因，不同的人对疾病的易感性差异很大。疾病易感性的潜在原因尚不清楚，但通常包括肺部的不同免疫反应。最近，我们发现了白细胞介素7受体(IL7R)在胎儿特异性肺巨噬细胞发育中的一个令人惊讶的新作用，IL7R是一种主要与淋巴相关的调节因子。在这里，我们报告了成人肺、外周血和骨髓中传统的造血干细胞来源的髓系细胞也依赖于IL7R的表达。采用单胚系和双胚系基因敲除模型，我们发现IL7Rα缺失后，嗜酸性粒细胞数量减少。然后，我们在谱系追踪实验中使用了两个Cre重组酶模型来测试这些细胞是否通过IL7Rα+途径发育。尽管有IL7Rα缺失的影响，IL7R-Cre只标记了极少量的嗜酸性粒细胞。因此，我们使用相互的造血干细胞移植试验研究了嗜酸性粒细胞产生过程中对IL7R的内在需求和外在需求。这些分析表明，成人肺HSC重建嗜酸性粒细胞需要外源性IL7R，而非嗜酸性粒细胞内源性IL7R。为了确定哪些外部因素可能影响嗜酸性粒细胞的发育和存活，我们在野生型和IL7Rα缺陷小鼠之间进行了细胞因子阵列分析，发现了几种差异调节的蛋白质。这些发现扩展了我们之前发表的文章，即IL7R不仅对正常的淋巴样细胞发育和稳态是必需的，而且对组织中的髓系细胞稳态也是必需的。
Respiratory diseases are a leading cause of death worldwide, with highly varied vulnerability to disease between individuals. The underlying reasons of disease susceptibility are unknown, but often include a variable immune response in lungs. Recently, we identified a surprising novel role of the interleukin 7 receptor (IL7R), a primarily lymphoid-associated regulator, in fetal-specified, lung-resident macrophage development. Here, we report that traditional, hematopoietic stem cell-derived myeloid cells in the adult lung, peripheral blood, and bone marrow also depend on IL7R expression. Using single and double germline knockout models, we found that eosinophil numbers were reduced upon deletion of IL7Rα. We then employed two Cre recombinase models in lineage tracing experiments to test whether these cells developed through an IL7Rα+ pathway. Despite the impact of IL7Rα deletion, IL7R-Cre labeled only a minimal fraction of eosinophils. We therefore examined the intrinsic versus extrinsic requirement for IL7R in the production of eosinophils using reciprocal hematopoietic stem cell transplantation assays. These assays revealed that extrinsic, but not eosinophil-intrinsic, IL7R is required for eosinophil reconstitution by HSCs in the adult lung. To determine which external factors may be influencing eosinophil development and survival, we performed a cytokine array analysis between wild-type and IL7Rα-deficient mice and found several differentially regulated proteins. These findings expand upon our previous publication that IL7R is required not only for proper lymphoid cell development and homeostasis, but also for myeloid cell homeostasis in tissues.
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白介素5缺乏消除小鼠哮喘模型中的嗜酸性粒细胞，气道高反应性和肺损伤。
影响因子：
15.3
作者：
Foster, PS;Hogan, SP;Ramsay, AJ;Matthaei, KI;Young, IG
通讯作者：
Young, IG
影响因子：
5.9
作者：
Smith-Berdan, Stephanie;Nguyen, Andrew;Hong, Matthew A.;Forsberg, E. Camilla
通讯作者：
Forsberg, E. Camilla
DOI：
10.4049/jimmunol.182.3.1404
发表时间：
2009-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kelly EA;Koziol-White CJ;Clay KJ;Liu LY;Bates ME;Bertics PJ;Jarjour NN
通讯作者：
Jarjour NN
影响因子：
32.4
作者：
Sawai CM;Babovic S;Upadhaya S;Knapp DJHF;Lavin Y;Lau CM;Goloborodko A;Feng J;Fujisaki J;Ding L;Mirny LA;Merad M;Eaves CJ;Reizis B
通讯作者：
Reizis B
影响因子：
5.9
作者：
Boyer, Scott W.;Rajendiran, Smrithi;Forsberg, E. Camilla
通讯作者：
Forsberg, E. Camilla