A Stromal Niche Defined by Expression of the Transcription Factor WT1 Mediates Programming and Homeostasis of Cavity-Resident Macrophages

Matthew B. Buechler; Ki Wook Kim; Emily J. Onufer; Jesse W. Williams; Christine C. Little; Claudia X. Dominguez; Qingling Li; Wendy Sandoval; Jonathan E. Cooper; Charles A. Harris; Melissa R. Junttila; Gwendalyn J. Randolph; Shannon J. Turley

doi:10.1016/j.immuni.2019.05.010

A Stromal Niche Defined by Expression of the Transcription Factor WT1 Mediates Programming and Homeostasis of Cavity-Resident Macrophages

Matthew B. Buechler, Ki Wook Kim, Emily J. Onufer, Jesse W. Williams, Christine C. Little, Claudia X. Dominguez, Qingling Li, Wendy Sandoval, Jonathan E. Cooper, Charles A. Harris, Melissa R. Junttila, Gwendalyn J. Randolph, Shannon J. Turley

Physiology

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101 Scopus citations

Abstract

Tissue-resident macrophages require specific milieus for the maintenance of defining gene-expression programs. Expression of the transcription factor GATA6 is required for the homeostasis, function and localization of peritoneal cavity-resident macrophages. Gata6 expression is maintained in a non-cell autonomous manner and is elicited by the vitamin A metabolite, retinoic acid. Here, we found that the GATA6 transcriptional program is a common feature of macrophages residing in all visceral body cavities. Retinoic acid-dependent and -independent hallmark genes of GATA6 + macrophages were induced by mesothelial and fibroblastic stromal cells that express the transcription factor Wilms' Tumor 1 (WT1), which drives the expression of two rate-limiting enzymes in retinol metabolism. Depletion of Wt1 + stromal cells reduced the frequency of GATA6 + macrophages in the peritoneal, pleural and pericardial cavities. Thus, Wt1 + mesothelial and fibroblastic stromal cells constitute essential niche components supporting the tissue-specifying transcriptional landscape and homeostasis of cavity-resident macrophages.

Original language	English (US)
Pages (from-to)	119-130.e5
Journal	Immunity
Volume	51
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2019.05.010
State	Published - Jul 16 2019

Bibliographical note

Funding Information:
We acknowledge members of the Turley and Randolph labs for their useful discussions and assistance in the laboratory. We thank facility staff at Genentech and Washington University in St. Louis for vivarium maintenance and core facility assistance and N.W. Lounsbury and S. Lianoglou for management of sequencing files. We express gratitude to A.M. Berkley for her careful review of this manuscript. We also acknowledge technical support from BioRender for the graphical abstract. This work was supported by Genentech, NIH grants R37 AI049653 and DP1DK109668 to G.J.R., K99 HL138163 to J.W.W., and T32 DK077653 to E.J.O.

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

Fibroblasts
Macrophages
Mesothelial cells
Retinoic acid
WT1
Mice, Inbred C57BL
Cells, Cultured
Homeostasis
Pleural Cavity/immunology
Mice, Transgenic
Peritoneal Cavity/physiology
GATA6 Transcription Factor/genetics
Stromal Cells/physiology
Repressor Proteins/genetics
Pericardium/immunology
Animals
Cell Differentiation
Mice
Macrophages/physiology
Tretinoin/metabolism

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1016/j.immuni.2019.05.010

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Buechler, M. B., Kim, K. W., Onufer, E. J., Williams, J. W., Little, C. C., Dominguez, C. X., Li, Q., Sandoval, W., Cooper, J. E., Harris, C. A., Junttila, M. R., Randolph, G. J., & Turley, S. J. (2019). A Stromal Niche Defined by Expression of the Transcription Factor WT1 Mediates Programming and Homeostasis of Cavity-Resident Macrophages. Immunity, 51(1), 119-130.e5. https://doi.org/10.1016/j.immuni.2019.05.010

Buechler, MB, Kim, KW, Onufer, EJ, Williams, JW, Little, CC, Dominguez, CX, Li, Q, Sandoval, W, Cooper, JE, Harris, CA, Junttila, MR, Randolph, GJ & Turley, SJ 2019, 'A Stromal Niche Defined by Expression of the Transcription Factor WT1 Mediates Programming and Homeostasis of Cavity-Resident Macrophages', Immunity, vol. 51, no. 1, pp. 119-130.e5. https://doi.org/10.1016/j.immuni.2019.05.010

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title = "A Stromal Niche Defined by Expression of the Transcription Factor WT1 Mediates Programming and Homeostasis of Cavity-Resident Macrophages",

abstract = "Tissue-resident macrophages require specific milieus for the maintenance of defining gene-expression programs. Expression of the transcription factor GATA6 is required for the homeostasis, function and localization of peritoneal cavity-resident macrophages. Gata6 expression is maintained in a non-cell autonomous manner and is elicited by the vitamin A metabolite, retinoic acid. Here, we found that the GATA6 transcriptional program is a common feature of macrophages residing in all visceral body cavities. Retinoic acid-dependent and -independent hallmark genes of GATA6 + macrophages were induced by mesothelial and fibroblastic stromal cells that express the transcription factor Wilms' Tumor 1 (WT1), which drives the expression of two rate-limiting enzymes in retinol metabolism. Depletion of Wt1 + stromal cells reduced the frequency of GATA6 + macrophages in the peritoneal, pleural and pericardial cavities. Thus, Wt1 + mesothelial and fibroblastic stromal cells constitute essential niche components supporting the tissue-specifying transcriptional landscape and homeostasis of cavity-resident macrophages. ",

keywords = "Fibroblasts, Macrophages, Mesothelial cells, Retinoic acid, WT1, Mice, Inbred C57BL, Cells, Cultured, Homeostasis, Pleural Cavity/immunology, Mice, Transgenic, Peritoneal Cavity/physiology, GATA6 Transcription Factor/genetics, Stromal Cells/physiology, Repressor Proteins/genetics, Pericardium/immunology, Animals, Cell Differentiation, Mice, Macrophages/physiology, Tretinoin/metabolism",

author = "Buechler, {Matthew B.} and Kim, {Ki Wook} and Onufer, {Emily J.} and Williams, {Jesse W.} and Little, {Christine C.} and Dominguez, {Claudia X.} and Qingling Li and Wendy Sandoval and Cooper, {Jonathan E.} and Harris, {Charles A.} and Junttila, {Melissa R.} and Randolph, {Gwendalyn J.} and Turley, {Shannon J.}",

note = "Funding Information: We acknowledge members of the Turley and Randolph labs for their useful discussions and assistance in the laboratory. We thank facility staff at Genentech and Washington University in St. Louis for vivarium maintenance and core facility assistance and N.W. Lounsbury and S. Lianoglou for management of sequencing files. We express gratitude to A.M. Berkley for her careful review of this manuscript. We also acknowledge technical support from BioRender for the graphical abstract. This work was supported by Genentech, NIH grants R37 AI049653 and DP1DK109668 to G.J.R., K99 HL138163 to J.W.W., and T32 DK077653 to E.J.O. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

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doi = "10.1016/j.immuni.2019.05.010",

language = "English (US)",

volume = "51",

pages = "119--130.e5",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "1",

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TY - JOUR

T1 - A Stromal Niche Defined by Expression of the Transcription Factor WT1 Mediates Programming and Homeostasis of Cavity-Resident Macrophages

AU - Buechler, Matthew B.

AU - Kim, Ki Wook

AU - Onufer, Emily J.

AU - Williams, Jesse W.

AU - Little, Christine C.

AU - Dominguez, Claudia X.

AU - Li, Qingling

AU - Sandoval, Wendy

AU - Cooper, Jonathan E.

AU - Harris, Charles A.

AU - Junttila, Melissa R.

AU - Randolph, Gwendalyn J.

AU - Turley, Shannon J.

N1 - Funding Information: We acknowledge members of the Turley and Randolph labs for their useful discussions and assistance in the laboratory. We thank facility staff at Genentech and Washington University in St. Louis for vivarium maintenance and core facility assistance and N.W. Lounsbury and S. Lianoglou for management of sequencing files. We express gratitude to A.M. Berkley for her careful review of this manuscript. We also acknowledge technical support from BioRender for the graphical abstract. This work was supported by Genentech, NIH grants R37 AI049653 and DP1DK109668 to G.J.R., K99 HL138163 to J.W.W., and T32 DK077653 to E.J.O. Publisher Copyright: © 2019 Elsevier Inc.

PY - 2019/7/16

Y1 - 2019/7/16

N2 - Tissue-resident macrophages require specific milieus for the maintenance of defining gene-expression programs. Expression of the transcription factor GATA6 is required for the homeostasis, function and localization of peritoneal cavity-resident macrophages. Gata6 expression is maintained in a non-cell autonomous manner and is elicited by the vitamin A metabolite, retinoic acid. Here, we found that the GATA6 transcriptional program is a common feature of macrophages residing in all visceral body cavities. Retinoic acid-dependent and -independent hallmark genes of GATA6 + macrophages were induced by mesothelial and fibroblastic stromal cells that express the transcription factor Wilms' Tumor 1 (WT1), which drives the expression of two rate-limiting enzymes in retinol metabolism. Depletion of Wt1 + stromal cells reduced the frequency of GATA6 + macrophages in the peritoneal, pleural and pericardial cavities. Thus, Wt1 + mesothelial and fibroblastic stromal cells constitute essential niche components supporting the tissue-specifying transcriptional landscape and homeostasis of cavity-resident macrophages.

AB - Tissue-resident macrophages require specific milieus for the maintenance of defining gene-expression programs. Expression of the transcription factor GATA6 is required for the homeostasis, function and localization of peritoneal cavity-resident macrophages. Gata6 expression is maintained in a non-cell autonomous manner and is elicited by the vitamin A metabolite, retinoic acid. Here, we found that the GATA6 transcriptional program is a common feature of macrophages residing in all visceral body cavities. Retinoic acid-dependent and -independent hallmark genes of GATA6 + macrophages were induced by mesothelial and fibroblastic stromal cells that express the transcription factor Wilms' Tumor 1 (WT1), which drives the expression of two rate-limiting enzymes in retinol metabolism. Depletion of Wt1 + stromal cells reduced the frequency of GATA6 + macrophages in the peritoneal, pleural and pericardial cavities. Thus, Wt1 + mesothelial and fibroblastic stromal cells constitute essential niche components supporting the tissue-specifying transcriptional landscape and homeostasis of cavity-resident macrophages.

KW - Fibroblasts

KW - Macrophages

KW - Mesothelial cells

KW - Retinoic acid

KW - WT1

KW - Mice, Inbred C57BL

KW - Cells, Cultured

KW - Homeostasis

KW - Pleural Cavity/immunology

KW - Mice, Transgenic

KW - Peritoneal Cavity/physiology

KW - GATA6 Transcription Factor/genetics

KW - Stromal Cells/physiology

KW - Repressor Proteins/genetics

KW - Pericardium/immunology

KW - Animals

KW - Cell Differentiation

KW - Mice

KW - Macrophages/physiology

KW - Tretinoin/metabolism

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UR - http://www.scopus.com/inward/citedby.url?scp=85068223107&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2019.05.010

DO - 10.1016/j.immuni.2019.05.010

M3 - Article

C2 - 31231034

AN - SCOPUS:85068223107

SN - 1074-7613

VL - 51

SP - 119-130.e5

JO - Immunity

JF - Immunity

IS - 1

ER -

A Stromal Niche Defined by Expression of the Transcription Factor WT1 Mediates Programming and Homeostasis of Cavity-Resident Macrophages

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

Publisher link

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