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

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

doi:10.1016/j.celrep.2022.110949

Cited by 25 publications

(21 citation statements)

References 68 publications

(80 reference statements)

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“…Our next objective was to establish the ontogeny of the priorly identified macrophage populations. First, using a single cell RNA seq dataset comprising CD45+ leukocytes in the adrenal gland 37 we used Lyz2 , Ccr2 , Cd68 and Cx3cr1 as myeloid markers and an unsupervised cell-type annotation tool 38 to filter 6,377 myeloid cells for downstream analyses. Further sub-clustering of these myeloid cells identified three distinct populations of myeloid cells in the adrenal gland (Fig.…”

Section: Resultsmentioning

confidence: 99%

Distinct adrenal gland macrophages regulate corticosteroid production

O’Brien,

Sidarta-Oliveira,

Stawiarski

et al. 2023

Preprint

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The adrenal glands are hormone secreting glands that sit on top of the kidneys. Adrenal glands produce glucocorticoids, mineralocorticoids, and catecholamines, and are therefore critical regulators of the stress response, the immune response, metabolism, and blood pressure. Despite being identified for more that 30 years, our understanding of adrenal macrophages remains incomplete. In numerous other tissues, macrophages carry out a plethora of physiological and homeostatic roles in addition to their classical immune functions. The aim of this study was to characterise the macrophage compartment of the adrenal gland and assess its contribution to adrenal function. Using an in vivo approach, we herein describe two morphologically and spatially distinct subsets of adrenal macrophages; dendritic-like macrophages that are present throughout the gland in young and old mice, and foamy lipid- laden macrophages that accumulate in the murine adrenal cortex in an age and diet-dependent manner. Furthermore, we present data showing that these foamy-like macrophages accumulate cholesterol and thereby regulate adrenal hormonal output, at steady state and in the context of obesity. We hereby provide novel insights into the physiological roles of macrophages in the adrenal gland and the mechanisms by which adrenal hormone production is regulated.

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Section: Resultsmentioning

confidence: 99%

Distinct adrenal gland macrophages regulate corticosteroid production

O’Brien,

Sidarta-Oliveira,

Stawiarski

et al. 2023

Preprint

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“…There have been numerous fate mapping studies of the origins and turnover of tissue-resident macrophages in various organs of the mouse, including studies of pancreas, thymus, testis, tongue and adrenal [27][28][29][30][31] since a previous review [2]. They include an analysis of skeletal muscle [32].…”

Section: The Interpretation Of Fate-mapping Studies In Micementioning

confidence: 99%

“…Diversity in turnover kinetics has also been described for sub-populations of macrophages defined by surface markers within individual tissues (e.g. [27,28,31]).…”

Section: The Interpretation Of Fate-mapping Studies In Micementioning

confidence: 99%

Fate‐mapping studies in inbred mice: A model for understanding macrophage development and homeostasis?

Hume

2023

Eur J Immunol

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The mononuclear phagocyte system (MPS) was defined in the early 1970s as a family of cells including progenitors, monocytes in the circulation, and resident tissue macrophages. They arise during development in three waves, in the yolk sac, fetal liver, and bone marrow. Fate-mapping studies using conditional reporter genes and regulated expression of cre recombinase have led to the view that most resident tissue macrophage populations are established during embryonic development and maintained in the adult by self-renewal with minimal input from bone marrow progenitors or blood monocytes. The interpretation of fate-mapping studies depends upon multiple assumptions: (i) that expression of cre recombinase has no effect on monocyte-macrophage homeostasis, (ii) that tamoxifen is a neutral agonist, (iii) that life in an SPF animal facility reflects the normal life course of a mouse, and (iv) that the C57Bl/6J inbred mouse is a generalizable model and the biology of the MPS is unaffected by mouse genetic background or species. This review summarizes evidence that questions each of these assumptions and concludes that fate-mapping studies may over-estimate the longevity and relative contribution of fetal-derived cells to resident tissue macrophage populations. In the opinion of the author, the original concept of the MPS does not require revision.

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“…To investigate the developmental origin of pancreatic tissue resident macrophages in PDA, we performed embryonic pulse chase experiments in tumor bearing CX3CR1 CreER R26 TdTomato mice. Given that CX3CR1 is turned on in embryonic derived macrophages during development 41 , in utero treatment of tamoxifen allows for robust and specific labeling of embryonic macrophages in these mice 38 . Pregnant CX3CR1 CreER R26 TdTomato mice were administered tamoxifen on embryonic day 14.5, then their progeny were implanted with tumors at 8 weeks of age then assessed 7 days post tumor (Figure 1M).…”

Section: Fate Mapping Of Monocyte Differentiation In Pdamentioning

confidence: 99%

“…Given that both monocyte-derived and embryonically-derived macrophages accumulate in PDA, distinguishing monocyte derived macrophages in vivo has been challenging. To overcome this, we utilized the CCR2 CreER R26 Tdtomato monocyte fate mapping mouse that allows for specific labeling of individual waves of blood monocytes following tamoxifen treatment, enabling tracking of their differentiation upon entry into tissue [37][38][39] . Tamoxifen treatment of CCR2 CreER R26 Tdtomato mice in steady state revealed robust classical monocyte labeling in the blood, but no labeling of pancreatic tissue resident macrophages (Supplemental figure 1A-D), consistent with their reported lack of Ccr2 expression 40 .…”

Section: Fate Mapping Of Monocyte Differentiation In Pdamentioning

confidence: 99%

Tumor-specific CD4 T cells instruct monocyte differentiation in pancreatic ductal adenocarcinoma

Patterson

Burrack

et al. 2022

Preprint

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Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy resistant to immunotherapy. The pancreatic tumor microenvironment is shaped and maintained by myeloid cells that outnumber tumor cells. Here, using monocyte fate-mapping PDA mouse models and human tumor tissues, we identify monocytes give rise to most heterogeneous macrophage subpopulations in PDA. We show that monocyte differentiation is governed by the local presence of CD4, but not CD8, T cells. We demonstrate that tumor specific CD4 T cells induce monocyte differentiation into antitumor MHCIIhi proinflammatory macrophages dependent on non-redundant IFNg and CD40 signaling pathways that suppress tumor growth. Pancreatic tissue-resident macrophages exhibit an immunosuppressive pro-tumor state that is refractory to the modulatory effects of antitumor CD4 T cells. Intratumoral monocytes adopt a pro-tumor fate indistinguishable from tissue-resident macrophages following CD4 T cell depletion. Thus, tumor-specific CD4 T cell governance of monocyte fate promotes immune-mediated control of solid tumors.

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

Cited by 25 publications

References 68 publications

Distinct adrenal gland macrophages regulate corticosteroid production

Distinct adrenal gland macrophages regulate corticosteroid production

Fate‐mapping studies in inbred mice: A model for understanding macrophage development and homeostasis?

Tumor-specific CD4 T cells instruct monocyte differentiation in pancreatic ductal adenocarcinoma

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