Unravelling the sex-specific diversity and functions of adrenal gland macrophages

Bastien Dolfi; Alexandre Gallerand; Maria M. Firulyova; Yingzheng Xu; Johanna Merlin; Adélie Dumont; Alexia Castiglione; Nathalie Vaillant; Sandrine Quemener; Heidi Gerke; Marion I. Stunault; Patricia R Schrank; Seung Hyeon Kim; Alisha Zhu; Jie Ding; Jerome Gilleron; Virginie Magnone; Pascal Barbry; David Dombrowicz; Christophe Duranton; Abdelilah Wakkach; Claudine Blin-Wakkach; Burkhard Becher; Sophie Pagnotta; Rafael J. Argüello; Pia Rantakari; Svetoslav Chakarov; Florent Ginhoux; Konstantin Zaitsev; Ki Wook Kim; Laurent Yvan-Charvet; Rodolphe R. Guinamard; Jesse W. Williams; Stoyan Ivanov

doi:10.1016/j.celrep.2022.110949

Unravelling the sex-specific diversity and functions of adrenal gland macrophages

Bastien Dolfi, Alexandre Gallerand, Maria M. Firulyova, Yingzheng Xu, Johanna Merlin, Adélie Dumont, Alexia Castiglione, Nathalie Vaillant, Sandrine Quemener, Heidi Gerke, Marion I. Stunault, Patricia R Schrank, Seung Hyeon Kim, Alisha Zhu, Jie Ding, Jerome Gilleron, Virginie Magnone, Pascal Barbry, David Dombrowicz, Christophe DurantonAbdelilah Wakkach, Claudine Blin-Wakkach, Burkhard Becher, Sophie Pagnotta, Rafael J. Argüello, Pia Rantakari, Svetoslav Chakarov, Florent Ginhoux, Konstantin Zaitsev, Ki Wook Kim, Laurent Yvan-Charvet, Rodolphe R. Guinamard, Jesse W. Williams, Stoyan Ivanov

Physiology

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

19 Scopus citations

Abstract

Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and use genetic models to explore the developmental mechanisms yielding macrophage diversity. We define populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identify a female-specific subset with low major histocompatibility complex (MHC) class II expression. In adulthood, monocyte recruitment dominates adrenal gland macrophage maintenance in female mice. Adrenal gland macrophage sub-tissular distribution follows a sex-dimorphic pattern, with MHC class II^low macrophages located at the cortico-medullary junction. Macrophage sex dimorphism depends on the presence of the cortical X-zone. Adrenal gland macrophage depletion results in altered tissue homeostasis, modulated lipid metabolism, and decreased local aldosterone production during stress exposure. Overall, these data reveal the heterogeneity of adrenal gland macrophages and point toward sex-restricted distribution and functions of these cells.

Original language	English (US)
Article number	110949
Journal	Cell reports
Volume	39
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2022.110949
State	Published - Jun 14 2022

Bibliographical note

Funding Information:
We would like to thank the C3M animal facility for technical support and the GIS-IBISA multi-sites platform Microscopie Imagerie Côte d'Azur (MICA), and particularly the imaging site of C3M supported by Conseil Régional, Conseil Départemental, and IBISA. We sincerely thank Narges Khedher and Marie Irondelle for their help. We would like to thank Fabien Labbal and Kevin Lebrigand and the UCA Genomix Platform. We acknowledge the flow cytometry facility from the “Institut de Pharmacologie Moléculaire et Cellulaire” part of the MICA GIS IBiSA labeled platform and the UMN flow cytometry core facility. A.G. was supported by the French government through the UCAJedi Investments in the Future projects managed by the National Research Agency ( ANR ) ( ANR-15-IDEX-01 ). M.M.F. and K.Z. were supported by Government of Russian Federation (grant 08–08 ). K.-W.K. is supported by NIH ( DK126753 ). R.R.G. is supported by Centre National de la Recherche Scientifique (CNRS). L.Y.-C. is supported by Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation de France ( 00066474 ), and the European Research Council (ERC) consolidator program ( ERC2016COG724838 ). J.W.W. was supported by National Institutes of Health ( HL138163 ) and American Heart Association ( CDA 855022 ). S.I. was supported by INSERM and Agence Nationale de la Recherche ( ANR-17-CE14-0017-01 and ANR-19-ECVD-0005-01 ). D.D. was supported by grants from the ANR and the European Union : EGID ANR-10-LABX-46 . R.J.A. was supported by ANR-20-CE-CE14-0028-01 and CoPoC MAT-PI-17493-A-04 .

Funding Information:
We would like to thank the C3M animal facility for technical support and the GIS-IBISA multi-sites platform Microscopie Imagerie Côte d'Azur (MICA), and particularly the imaging site of C3M supported by Conseil Régional, Conseil Départemental, and IBISA. We sincerely thank Narges Khedher and Marie Irondelle for their help. We would like to thank Fabien Labbal and Kevin Lebrigand and the UCA Genomix Platform. We acknowledge the flow cytometry facility from the “Institut de Pharmacologie Moléculaire et Cellulaire” part of the MICA GIS IBiSA labeled platform and the UMN flow cytometry core facility. A.G. was supported by the French government through the UCAJedi Investments in the Future projects managed by the National Research Agency (ANR) (ANR-15-IDEX-01). M.M.F. and K.Z. were supported by Government of Russian Federation (grant 08–08). K.-W.K. is supported by NIH (DK126753). R.R.G. is supported by Centre National de la Recherche Scientifique (CNRS). L.Y.-C. is supported by Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation de France (00066474), and the European Research Council (ERC) consolidator program (ERC2016COG724838). J.W.W. was supported by National Institutes of Health (HL138163) and American Heart Association (CDA 855022). S.I. was supported by INSERM and Agence Nationale de la Recherche (ANR-17-CE14-0017-01 and ANR-19-ECVD-0005-01). D.D. was supported by grants from the ANR and the European Union: EGID ANR-10-LABX-46. R.J.A. was supported by ANR-20-CE-CE14-0028-01 and CoPoC MAT-PI-17493-A-04. S.I. J.W.W. and R.R.G. conceptualized the study. B.D. A.G. Y.X. J.M. A.D. A.C. N.V. S.Q. H.G. M.I.S. P.R.S. S.-H.K. A.Z. J.D. J.G. V.M. P.B. C.D. A.W. C.B.-W. S.P. S.C. K.-W.K. L.Y.-C. R.R.G. J.W.W. and S.I. performed experiments, analyzed the data, and edited the manuscript. B.D. A.G. R.R.G. J.W.W. and S.I. wrote the manuscript. M.M.F. and K.Z. performed the analysis of the scRNA-seq data and bulk RNA-seq data and wrote and edited the manuscript. D.D. B.B. R.J.A. P.R. and F.G. provided tools and expertise and edited the manuscript. The authors declare no competing interests.

Publisher Copyright:
© 2022 The Author(s)

Keywords

CP: Immunology
adrenal gland
macrophage
monocyte
sex dimorphism

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10.1016/j.celrep.2022.110949

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Dolfi, B., Gallerand, A., Firulyova, M. M., Xu, Y., Merlin, J., Dumont, A., Castiglione, A., Vaillant, N., Quemener, S., Gerke, H., Stunault, M. I., Schrank, P. R., Kim, S. H., Zhu, A., Ding, J., Gilleron, J., Magnone, V., Barbry, P., Dombrowicz, D., ... Ivanov, S. (2022). Unravelling the sex-specific diversity and functions of adrenal gland macrophages. Cell reports, 39(11), Article 110949. https://doi.org/10.1016/j.celrep.2022.110949

Dolfi, B, Gallerand, A, Firulyova, MM, Xu, Y, Merlin, J, Dumont, A, Castiglione, A, Vaillant, N, Quemener, S, Gerke, H, Stunault, MI, Schrank, PR, Kim, SH, Zhu, A, Ding, J, Gilleron, J, Magnone, V, Barbry, P, Dombrowicz, D, Duranton, C, Wakkach, A, Blin-Wakkach, C, Becher, B, Pagnotta, S, Argüello, RJ, Rantakari, P, Chakarov, S, Ginhoux, F, Zaitsev, K, Kim, KW, Yvan-Charvet, L, Guinamard, RR, Williams, JW & Ivanov, S 2022, 'Unravelling the sex-specific diversity and functions of adrenal gland macrophages', Cell reports, vol. 39, no. 11, 110949. https://doi.org/10.1016/j.celrep.2022.110949

@article{f6cb9516432d4bbbb0d624c6abf67b56,

title = "Unravelling the sex-specific diversity and functions of adrenal gland macrophages",

abstract = "Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and use genetic models to explore the developmental mechanisms yielding macrophage diversity. We define populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identify a female-specific subset with low major histocompatibility complex (MHC) class II expression. In adulthood, monocyte recruitment dominates adrenal gland macrophage maintenance in female mice. Adrenal gland macrophage sub-tissular distribution follows a sex-dimorphic pattern, with MHC class IIlow macrophages located at the cortico-medullary junction. Macrophage sex dimorphism depends on the presence of the cortical X-zone. Adrenal gland macrophage depletion results in altered tissue homeostasis, modulated lipid metabolism, and decreased local aldosterone production during stress exposure. Overall, these data reveal the heterogeneity of adrenal gland macrophages and point toward sex-restricted distribution and functions of these cells.",

keywords = "CP: Immunology, adrenal gland, macrophage, monocyte, sex dimorphism",

author = "Bastien Dolfi and Alexandre Gallerand and Firulyova, {Maria M.} and Yingzheng Xu and Johanna Merlin and Ad{\'e}lie Dumont and Alexia Castiglione and Nathalie Vaillant and Sandrine Quemener and Heidi Gerke and Stunault, {Marion I.} and Schrank, {Patricia R} and Kim, {Seung Hyeon} and Alisha Zhu and Jie Ding and Jerome Gilleron and Virginie Magnone and Pascal Barbry and David Dombrowicz and Christophe Duranton and Abdelilah Wakkach and Claudine Blin-Wakkach and Burkhard Becher and Sophie Pagnotta and Arg{\"u}ello, {Rafael J.} and Pia Rantakari and Svetoslav Chakarov and Florent Ginhoux and Konstantin Zaitsev and Kim, {Ki Wook} and Laurent Yvan-Charvet and Guinamard, {Rodolphe R.} and Williams, {Jesse W.} and Stoyan Ivanov",

note = "Funding Information: We would like to thank the C3M animal facility for technical support and the GIS-IBISA multi-sites platform Microscopie Imagerie C{\^o}te d'Azur (MICA), and particularly the imaging site of C3M supported by Conseil R{\'e}gional, Conseil D{\'e}partemental, and IBISA. We sincerely thank Narges Khedher and Marie Irondelle for their help. We would like to thank Fabien Labbal and Kevin Lebrigand and the UCA Genomix Platform. We acknowledge the flow cytometry facility from the “Institut de Pharmacologie Mol{\'e}culaire et Cellulaire” part of the MICA GIS IBiSA labeled platform and the UMN flow cytometry core facility. A.G. was supported by the French government through the UCAJedi Investments in the Future projects managed by the National Research Agency ( ANR ) ( ANR-15-IDEX-01 ). M.M.F. and K.Z. were supported by Government of Russian Federation (grant 08–08 ). K.-W.K. is supported by NIH ( DK126753 ). R.R.G. is supported by Centre National de la Recherche Scientifique (CNRS). L.Y.-C. is supported by Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (INSERM), Fondation de France ( 00066474 ), and the European Research Council (ERC) consolidator program ( ERC2016COG724838 ). J.W.W. was supported by National Institutes of Health ( HL138163 ) and American Heart Association ( CDA 855022 ). S.I. was supported by INSERM and Agence Nationale de la Recherche ( ANR-17-CE14-0017-01 and ANR-19-ECVD-0005-01 ). D.D. was supported by grants from the ANR and the European Union : EGID ANR-10-LABX-46 . R.J.A. was supported by ANR-20-CE-CE14-0028-01 and CoPoC MAT-PI-17493-A-04 . Funding Information: We would like to thank the C3M animal facility for technical support and the GIS-IBISA multi-sites platform Microscopie Imagerie C{\^o}te d'Azur (MICA), and particularly the imaging site of C3M supported by Conseil R{\'e}gional, Conseil D{\'e}partemental, and IBISA. We sincerely thank Narges Khedher and Marie Irondelle for their help. We would like to thank Fabien Labbal and Kevin Lebrigand and the UCA Genomix Platform. We acknowledge the flow cytometry facility from the “Institut de Pharmacologie Mol{\'e}culaire et Cellulaire” part of the MICA GIS IBiSA labeled platform and the UMN flow cytometry core facility. A.G. was supported by the French government through the UCAJedi Investments in the Future projects managed by the National Research Agency (ANR) (ANR-15-IDEX-01). M.M.F. and K.Z. were supported by Government of Russian Federation (grant 08–08). K.-W.K. is supported by NIH (DK126753). R.R.G. is supported by Centre National de la Recherche Scientifique (CNRS). L.Y.-C. is supported by Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (INSERM), Fondation de France (00066474), and the European Research Council (ERC) consolidator program (ERC2016COG724838). J.W.W. was supported by National Institutes of Health (HL138163) and American Heart Association (CDA 855022). S.I. was supported by INSERM and Agence Nationale de la Recherche (ANR-17-CE14-0017-01 and ANR-19-ECVD-0005-01). D.D. was supported by grants from the ANR and the European Union: EGID ANR-10-LABX-46. R.J.A. was supported by ANR-20-CE-CE14-0028-01 and CoPoC MAT-PI-17493-A-04. S.I. J.W.W. and R.R.G. conceptualized the study. B.D. A.G. Y.X. J.M. A.D. A.C. N.V. S.Q. H.G. M.I.S. P.R.S. S.-H.K. A.Z. J.D. J.G. V.M. P.B. C.D. A.W. C.B.-W. S.P. S.C. K.-W.K. L.Y.-C. R.R.G. J.W.W. and S.I. performed experiments, analyzed the data, and edited the manuscript. B.D. A.G. R.R.G. J.W.W. and S.I. wrote the manuscript. M.M.F. and K.Z. performed the analysis of the scRNA-seq data and bulk RNA-seq data and wrote and edited the manuscript. D.D. B.B. R.J.A. P.R. and F.G. provided tools and expertise and edited the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = jun,

day = "14",

doi = "10.1016/j.celrep.2022.110949",

language = "English (US)",

volume = "39",

journal = "Cell reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "11",

}

TY - JOUR

T1 - Unravelling the sex-specific diversity and functions of adrenal gland macrophages

AU - Dolfi, Bastien

AU - Gallerand, Alexandre

AU - Firulyova, Maria M.

AU - Xu, Yingzheng

AU - Merlin, Johanna

AU - Dumont, Adélie

AU - Castiglione, Alexia

AU - Vaillant, Nathalie

AU - Quemener, Sandrine

AU - Gerke, Heidi

AU - Stunault, Marion I.

AU - Schrank, Patricia R

AU - Kim, Seung Hyeon

AU - Zhu, Alisha

AU - Ding, Jie

AU - Gilleron, Jerome

AU - Magnone, Virginie

AU - Barbry, Pascal

AU - Dombrowicz, David

AU - Duranton, Christophe

AU - Wakkach, Abdelilah

AU - Blin-Wakkach, Claudine

AU - Becher, Burkhard

AU - Pagnotta, Sophie

AU - Argüello, Rafael J.

AU - Rantakari, Pia

AU - Chakarov, Svetoslav

AU - Ginhoux, Florent

AU - Zaitsev, Konstantin

AU - Kim, Ki Wook

AU - Yvan-Charvet, Laurent

AU - Guinamard, Rodolphe R.

AU - Williams, Jesse W.

AU - Ivanov, Stoyan

N1 - Funding Information: We would like to thank the C3M animal facility for technical support and the GIS-IBISA multi-sites platform Microscopie Imagerie Côte d'Azur (MICA), and particularly the imaging site of C3M supported by Conseil Régional, Conseil Départemental, and IBISA. We sincerely thank Narges Khedher and Marie Irondelle for their help. We would like to thank Fabien Labbal and Kevin Lebrigand and the UCA Genomix Platform. We acknowledge the flow cytometry facility from the “Institut de Pharmacologie Moléculaire et Cellulaire” part of the MICA GIS IBiSA labeled platform and the UMN flow cytometry core facility. A.G. was supported by the French government through the UCAJedi Investments in the Future projects managed by the National Research Agency ( ANR ) ( ANR-15-IDEX-01 ). M.M.F. and K.Z. were supported by Government of Russian Federation (grant 08–08 ). K.-W.K. is supported by NIH ( DK126753 ). R.R.G. is supported by Centre National de la Recherche Scientifique (CNRS). L.Y.-C. is supported by Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation de France ( 00066474 ), and the European Research Council (ERC) consolidator program ( ERC2016COG724838 ). J.W.W. was supported by National Institutes of Health ( HL138163 ) and American Heart Association ( CDA 855022 ). S.I. was supported by INSERM and Agence Nationale de la Recherche ( ANR-17-CE14-0017-01 and ANR-19-ECVD-0005-01 ). D.D. was supported by grants from the ANR and the European Union : EGID ANR-10-LABX-46 . R.J.A. was supported by ANR-20-CE-CE14-0028-01 and CoPoC MAT-PI-17493-A-04 . Funding Information: We would like to thank the C3M animal facility for technical support and the GIS-IBISA multi-sites platform Microscopie Imagerie Côte d'Azur (MICA), and particularly the imaging site of C3M supported by Conseil Régional, Conseil Départemental, and IBISA. We sincerely thank Narges Khedher and Marie Irondelle for their help. We would like to thank Fabien Labbal and Kevin Lebrigand and the UCA Genomix Platform. We acknowledge the flow cytometry facility from the “Institut de Pharmacologie Moléculaire et Cellulaire” part of the MICA GIS IBiSA labeled platform and the UMN flow cytometry core facility. A.G. was supported by the French government through the UCAJedi Investments in the Future projects managed by the National Research Agency (ANR) (ANR-15-IDEX-01). M.M.F. and K.Z. were supported by Government of Russian Federation (grant 08–08). K.-W.K. is supported by NIH (DK126753). R.R.G. is supported by Centre National de la Recherche Scientifique (CNRS). L.Y.-C. is supported by Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation de France (00066474), and the European Research Council (ERC) consolidator program (ERC2016COG724838). J.W.W. was supported by National Institutes of Health (HL138163) and American Heart Association (CDA 855022). S.I. was supported by INSERM and Agence Nationale de la Recherche (ANR-17-CE14-0017-01 and ANR-19-ECVD-0005-01). D.D. was supported by grants from the ANR and the European Union: EGID ANR-10-LABX-46. R.J.A. was supported by ANR-20-CE-CE14-0028-01 and CoPoC MAT-PI-17493-A-04. S.I. J.W.W. and R.R.G. conceptualized the study. B.D. A.G. Y.X. J.M. A.D. A.C. N.V. S.Q. H.G. M.I.S. P.R.S. S.-H.K. A.Z. J.D. J.G. V.M. P.B. C.D. A.W. C.B.-W. S.P. S.C. K.-W.K. L.Y.-C. R.R.G. J.W.W. and S.I. performed experiments, analyzed the data, and edited the manuscript. B.D. A.G. R.R.G. J.W.W. and S.I. wrote the manuscript. M.M.F. and K.Z. performed the analysis of the scRNA-seq data and bulk RNA-seq data and wrote and edited the manuscript. D.D. B.B. R.J.A. P.R. and F.G. provided tools and expertise and edited the manuscript. The authors declare no competing interests. Publisher Copyright: © 2022 The Author(s)

PY - 2022/6/14

Y1 - 2022/6/14

N2 - Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and use genetic models to explore the developmental mechanisms yielding macrophage diversity. We define populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identify a female-specific subset with low major histocompatibility complex (MHC) class II expression. In adulthood, monocyte recruitment dominates adrenal gland macrophage maintenance in female mice. Adrenal gland macrophage sub-tissular distribution follows a sex-dimorphic pattern, with MHC class IIlow macrophages located at the cortico-medullary junction. Macrophage sex dimorphism depends on the presence of the cortical X-zone. Adrenal gland macrophage depletion results in altered tissue homeostasis, modulated lipid metabolism, and decreased local aldosterone production during stress exposure. Overall, these data reveal the heterogeneity of adrenal gland macrophages and point toward sex-restricted distribution and functions of these cells.

AB - Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and use genetic models to explore the developmental mechanisms yielding macrophage diversity. We define populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identify a female-specific subset with low major histocompatibility complex (MHC) class II expression. In adulthood, monocyte recruitment dominates adrenal gland macrophage maintenance in female mice. Adrenal gland macrophage sub-tissular distribution follows a sex-dimorphic pattern, with MHC class IIlow macrophages located at the cortico-medullary junction. Macrophage sex dimorphism depends on the presence of the cortical X-zone. Adrenal gland macrophage depletion results in altered tissue homeostasis, modulated lipid metabolism, and decreased local aldosterone production during stress exposure. Overall, these data reveal the heterogeneity of adrenal gland macrophages and point toward sex-restricted distribution and functions of these cells.

KW - CP: Immunology

KW - adrenal gland

KW - macrophage

KW - monocyte

KW - sex dimorphism

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UR - http://www.scopus.com/inward/citedby.url?scp=85131969315&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2022.110949

DO - 10.1016/j.celrep.2022.110949

M3 - Article

C2 - 35705045

AN - SCOPUS:85131969315

SN - 2211-1247

VL - 39

JO - Cell reports

JF - Cell reports

IS - 11

M1 - 110949

ER -

Unravelling the sex-specific diversity and functions of adrenal gland macrophages

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