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 Dutton; Muath Suliman; Alice E Denton; Shannon J Turley; Richard L. Boyd; Scott Norman 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 Dutton, Muath Suliman, Alice E Denton, Shannon J Turley, Richard L. Boyd, Scott Norman Mueller, Burkhard Ludewig, Tracy S.P. Heng, Anne L. Fletcher

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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
Number of pages	14
Journal	European Journal of Immunology
Volume	53
Issue number	9
DOIs	https://doi.org/10.1002/eji.202250355
Publication status	Published - Sept 2023

Keywords

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

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10.1002/eji.202250355Licence: CC BY

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D'Rozario, J., Knoblich, K., Lütge, M., Pérez Shibayama, C., Cheng, H.-W., Alexandre, Y. O., Roberts, D., Campos, J., Dutton, 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, 53(9), Article 2250355. https://doi.org/10.1002/eji.202250355

@article{22f35aeb840941779ac8f9817ad160e8,

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

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

note = "Funding Information: This work was supported by a Wellcome Trust Seed Award to A.F. (109783/Z/15/Z). A.F. was supported by a Birmingham Fellowship, a Monash Biomedicine Discovery Institute Fellowship, and an NHMRC Ideas Grant (GNT2004253). T.S.P.H. was supported by the National Health and Medical Research Council of Australia (GNT1107188, GNT1162499, GNT2012290) and the Australian Research Council (IC190100026). The authors thank D. Fearon for DM2 mice. We acknowledge the University of Birmingham's Human Biomaterials Resource Centre, supported through a Birmingham Science City - Experimental Medicine Network of Excellence project. Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians. Funding Information: This work was supported by a Wellcome Trust Seed Award to A.F. (109783/Z/15/Z). A.F. was supported by a Birmingham Fellowship, a Monash Biomedicine Discovery Institute Fellowship, and an NHMRC Ideas Grant (GNT2004253). T.S.P.H. was supported by the National Health and Medical Research Council of Australia (GNT1107188, GNT1162499, GNT2012290) and the Australian Research Council (IC190100026). The authors thank D. Fearon for DM2 mice. We acknowledge the University of Birmingham's Human Biomaterials Resource Centre, supported through a Birmingham Science City ‐‐ Experimental Medicine Network of Excellence project. Publisher Copyright: {\textcopyright} 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.",

year = "2023",

month = sep,

doi = "10.1002/eji.202250355",

language = "English",

volume = "53",

journal = "European Journal of Immunology",

issn = "0014-2980",

publisher = "Wiley-VCH Verlag GmbH & Co. KGaA",

number = "9",

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D'Rozario, J, Knoblich, K, Lütge, M, Pérez Shibayama, C, Cheng, H-W, Alexandre, YO, Roberts, D, Campos, J, Dutton, E, 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, vol. 53, no. 9, 2250355. 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 - Pérez Shibayama, Christian

AU - Cheng, Hung-Wei

AU - Alexandre, Yannick O.

AU - Roberts, David

AU - Campos, Joana

AU - Dutton, Emma

AU - Suliman, Muath

AU - Denton, Alice E

AU - Turley, Shannon J

AU - Boyd, Richard L.

AU - Mueller, Scott Norman

AU - Ludewig, Burkhard

AU - Heng, Tracy S.P.

AU - Fletcher, Anne L.

N1 - Funding Information: This work was supported by a Wellcome Trust Seed Award to A.F. (109783/Z/15/Z). A.F. was supported by a Birmingham Fellowship, a Monash Biomedicine Discovery Institute Fellowship, and an NHMRC Ideas Grant (GNT2004253). T.S.P.H. was supported by the National Health and Medical Research Council of Australia (GNT1107188, GNT1162499, GNT2012290) and the Australian Research Council (IC190100026). The authors thank D. Fearon for DM2 mice. We acknowledge the University of Birmingham's Human Biomaterials Resource Centre, supported through a Birmingham Science City - Experimental Medicine Network of Excellence project. Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians. Funding Information: This work was supported by a Wellcome Trust Seed Award to A.F. (109783/Z/15/Z). A.F. was supported by a Birmingham Fellowship, a Monash Biomedicine Discovery Institute Fellowship, and an NHMRC Ideas Grant (GNT2004253). T.S.P.H. was supported by the National Health and Medical Research Council of Australia (GNT1107188, GNT1162499, GNT2012290) and the Australian Research Council (IC190100026). The authors thank D. Fearon for DM2 mice. We acknowledge the University of Birmingham's Human Biomaterials Resource Centre, supported through a Birmingham Science City ‐‐ Experimental Medicine Network of Excellence project. Publisher Copyright: © 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.

PY - 2023/9

Y1 - 2023/9

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 - CSF1

KW - Fibroblastic reticular cells

KW - Human lymph nodes

KW - Lymph node stromal cells

KW - Macrophages

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U2 - 10.1002/eji.202250355

DO - 10.1002/eji.202250355

M3 - Article

C2 - 36991561

AN - SCOPUS:85165175372

SN - 0014-2980

VL - 53

JO - European Journal of Immunology

JF - European Journal of Immunology

IS - 9

M1 - 2250355

ER -

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

Abstract

Keywords

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