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

Joshua D'Rozario; Konstantin Knoblich; Mechthild Lütge; Christian Pérez Shibayama; Hung‐Wei Cheng; Yannick O. Alexandre; David Roberts; Joana Campos; Emma E. Dutton; Muath Suliman; Alice E. Denton; Shannon J. Turley; Richard L. Boyd; Scott N. Mueller; Burkhard Ludewig; Tracy S.P. Heng; Anne L. Fletcher

doi:10.1002/eji.202250355

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

Joshua D'Rozario, Konstantin Knoblich, Mechthild Lütge, Christian Pérez Shibayama, Hung‐Wei Cheng, Yannick O. Alexandre, David Roberts, Joana Campos, Emma E. Dutton, Muath Suliman, Alice E. Denton, Shannon J. Turley, Richard L. Boyd, Scott N. Mueller, Burkhard Ludewig, Tracy S.P. Heng^*, Anne L. Fletcher^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Article number	2250355
Journal	European Journal of Immunology
Early online date	12 Jul 2023
DOIs	https://doi.org/10.1002/eji.202250355
Publication status	E-pub ahead of print - 12 Jul 2023

Keywords

Human lymph nodes
Lymph node stromal cells
Fibroblastic reticular cells
Macrophages
CSF1

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D'Rozario, J., Knoblich, K., Lütge, M., Shibayama, C. P., Cheng, HW., Alexandre, Y. O., Roberts, D., Campos, J., Dutton, E. E., Suliman, M., Denton, A. E., Turley, S. J., Boyd, R. L., Mueller, S. N., Ludewig, B., Heng, T. S. P., & Fletcher, A. L. (2023). Fibroblastic reticular cells provide a supportive niche for lymph node–resident macrophages. European Journal of Immunology, Article 2250355. Advance online publication. https://doi.org/10.1002/eji.202250355

@article{c7197688c40e44709cfcc2b729835100,

title = "Fibroblastic reticular cells provide a supportive niche for lymph node–resident macrophages",

abstract = "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.",

keywords = "Human lymph nodes, Lymph node stromal cells, Fibroblastic reticular cells, Macrophages, CSF1",

author = "Joshua D'Rozario and Konstantin Knoblich and Mechthild L{\"u}tge and Shibayama, {Christian P{\'e}rez} and Hung‐Wei Cheng and Alexandre, {Yannick O.} and David Roberts and Joana Campos and Dutton, {Emma E.} and Muath Suliman and Denton, {Alice E.} and Turley, {Shannon J.} and Boyd, {Richard L.} and Mueller, {Scott N.} and Burkhard Ludewig and Heng, {Tracy S.P.} and Fletcher, {Anne L.}",

year = "2023",

month = jul,

day = "12",

doi = "10.1002/eji.202250355",

language = "English",

journal = "European Journal of Immunology",

issn = "0014-2980",

publisher = "Wiley-VCH Verlag",

}

D'Rozario, J, Knoblich, K, Lütge, M, Shibayama, CP, Cheng, HW, Alexandre, YO, Roberts, D, Campos, J, Dutton, EE, Suliman, M, Denton, AE, Turley, SJ, Boyd, RL, Mueller, SN, Ludewig, B, Heng, TSP & Fletcher, AL 2023, 'Fibroblastic reticular cells provide a supportive niche for lymph node–resident macrophages', European Journal of Immunology. https://doi.org/10.1002/eji.202250355

TY - JOUR

T1 - Fibroblastic reticular cells provide a supportive niche for lymph node–resident macrophages

AU - D'Rozario, Joshua

AU - Knoblich, Konstantin

AU - Lütge, Mechthild

AU - Shibayama, Christian Pérez

AU - Cheng, Hung‐Wei

AU - Alexandre, Yannick O.

AU - Roberts, David

AU - Campos, Joana

AU - Dutton, Emma E.

AU - Suliman, Muath

AU - Denton, Alice E.

AU - Turley, Shannon J.

AU - Boyd, Richard L.

AU - Mueller, Scott N.

AU - Ludewig, Burkhard

AU - Heng, Tracy S.P.

AU - Fletcher, Anne L.

PY - 2023/7/12

Y1 - 2023/7/12

N2 - 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.

AB - 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.

KW - Human lymph nodes

KW - Lymph node stromal cells

KW - Fibroblastic reticular cells

KW - Macrophages

KW - CSF1

U2 - 10.1002/eji.202250355

DO - 10.1002/eji.202250355

M3 - Article

SN - 0014-2980

JO - European Journal of Immunology

JF - European Journal of Immunology

M1 - 2250355

ER -

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

Abstract

Keywords

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