Fibroblastic reticular cells provide a supportive niche for lymph node-resident macrophages

被引:10
|
作者
D'Rozario, Joshua [1 ,2 ,3 ,4 ]
Knoblich, Konstantin [1 ,2 ,4 ]
Luetge, Mechthild [5 ]
Shibayama, Christian Perez [5 ]
Cheng, Hung-Wei [5 ]
Alexandre, Yannick O. [6 ]
Roberts, David [4 ]
Campos, Joana [7 ]
Dutton, Emma E. [4 ]
Suliman, Muath [4 ]
Denton, Alice E. [8 ]
Turley, Shannon J. [9 ]
Boyd, Richard L. [10 ]
Mueller, Scott N. [6 ]
Ludewig, Burkhard [5 ]
Heng, Tracy S. P. [3 ,11 ]
Fletcher, Anne L. [1 ,2 ,4 ]
机构
[1] Monash Univ, Dept Biochem & Mol Biol, Clayton, Australia
[2] Monash Univ, Monash Biomed Discovery Inst, Clayton, Australia
[3] Monash Univ, Monash Biomed Discovery Inst, Dept Anat & Dev Biol, Clayton, Australia
[4] Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham, England
[5] Kantonsspital St Gallen, Inst Immunobiol, St Gallen, Switzerland
[6] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, VIC, Australia
[7] Univ Birmingham, Inst Inflammat & Ageing, Birmingham, England
[8] Imperial Coll London, Dept Immunol & Inflammat, London, England
[9] Genentech Inc, Dept Canc Immunol, South San Francisco, CA USA
[10] Carther Pty Ltd, Hudson Inst Med Res, Clayton, Australia
[11] Monash Univ, ARC Training Ctr Cell & Tissue Engn Technol, Clayton, Australia
基金
澳大利亚研究理事会; 英国医学研究理事会; 英国惠康基金; 澳大利亚国家健康与医学研究理事会;
关键词
CSF1; Fibroblastic reticular cells; Human lymph nodes; Lymph node stromal cells; Macrophages; SUBCAPSULAR SINUS MACROPHAGES; STIMULATING FACTOR-I; DENDRITIC CELLS; ACTIVATION; MONOCYTES; ANTIGEN; TISSUE; HOMEOSTASIS; INFECTION; FOLLICLE;
D O I
10.1002/eji.202250355
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis, but key factors controlling this niche are undefined. Here, we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Genetic ablation of FRCs caused rapid loss of macrophages and monocytes from LNs across two in vivo models. Macrophages co-localized with FRCs in human LNs, and murine single-cell RNA-sequencing revealed that FRC subsets broadly expressed master macrophage regulator CSF1. Functional assays containing purified FRCs and monocytes showed that CSF1R signaling was sufficient to support macrophage development. These effects were conserved between mouse and human systems. These data indicate an important role for FRCs in maintaining the LN parenchymal macrophage niche.
引用
收藏
页数:14
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