Human Dermal CD14 + Cells Are a Transient Population of Monocyte-Derived Macrophages

McGovern, Naomi; Schlitzer, Andreas; Gunawan, Merry; Jardine, Laura; Shin, Amanda; Poyner, Elizabeth; Green, Kile; Dickinson, Rachel; Wang, Xiao-Nong; Low, Donovan; Best, Katie; Covins, Samuel; Milne, Paul; Pagan, Sarah; Aljefri, K; Windebank, Martin; Miranda‐Saavedra, Diego; Larbi, Anis; Wasan, Pavandip Singh; Duan, Kaibo; Poidinger, Michael; Bigley, Venetia; Ginhoux, Florent; Collin, Matthew; Haniffa, Muzlifah

doi:10.1016/j.immuni.2014.08.006

Cited by 246 publications

(293 citation statements)

References 53 publications

(75 reference statements)

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“…1f). These data extend recent observations that resident macrophages in some tissues express Zbtb46 19 , and showed that the amount of Zbtb46 expression, as inferred from the GFP reporter, discriminated between macrophages and cDC in the arterial wall. cDC were also distinguished from macrophages by expression of the integrin alpha X (CD11c) (Fig.…”

Section: Cd11bsupporting

confidence: 89%

Self-renewing resident arterial macrophages arise from embryonic CX3CR1+ precursors and circulating monocytes immediately after birth

et al. 2015

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Most tissues of the body harbor resident macrophages. Yet, macrophages are phenotypically and functionally heterogeneous, a reflection of the diversity of tissue environments in which they reside. In addition to maintaining tissue homeostasis and responding to invading pathogens, macrophages contribute to numerous pathological processes, making them an attractive potential target for therapeutic intervention. To do so, however, will require a detailed understanding of macrophage origins, the mechanisms that maintain them, and their functional attributes in different tissues and disease contexts.Macrophage ontology has long engendered controversy 1,2 . Nevertheless, the concept that tissue macrophages develop exclusively from circulating bone marrow-derived monocytes has prevailed for nearly a half century 3 . Accumulated evidence, however, including recent studies using sophisticated fate-mapping approaches, have determined that some tissue macrophages and their precursors are established embryonically in the yolk sac (YS) and fetal liver before the onset of definitive hematopoiesis [4][5][6][7][8][9][10][11] . Regardless of their origin, tissue macrophages can maintain themselves in adulthood by self-renewal independent of blood monocytes 12,13 .Gene-expression profiling of macrophage populations from several tissues has established that only a small number of transcripts are expressed by all macrophages 14 , indicating the importance of the context provided by the tissue when studying macrophage function in homeostasis and disease. The normal arterial wall contains many tissue resident macrophages that contribute crucially to immunity, tissue homeostasis and wound healing following injury 15. However, the regulatory networks, ancestry and mechanisms that maintain arterial macrophages remain unknown.Using gene expression analysis, we show that arterial macrophages constitute a distinct population among tissue macrophages. Multiple fate mapping approaches demonstrated that arterial macrophages arise embryonically from CX 3 CR1 + precursors and postnatally from bone marrow-derived monocytes that colonize the tissue during a brief period immediately after birth.In adulthood, arterial macrophages were maintained by CX 3 CR1-CX 3 CL1 interactions and local proliferation without significant further contribution from blood monocytes. Self-renewal also sustained arterial macrophages after severe depletion during polymicrobial sepsis, rapidly restoring them to functional homeostasis. ResultsPhenotype and gene expression profiling of arterial macrophages. (Fig. 1a).Principal component analysis revealed a distinct transcriptome in arterial macrophages, which clustered near other macrophage populations including microglia, alveolar macrophages, and splenic red pulp macrophages, as characterized by the Immunological Genome Consortium (Fig. 1b, Supplementary Fig. 1a) 14. Stringent comparison of gene-expression profiles among arterial, brain, alveolar and splenic red pulp macrophages revealed 212 transcripts that were at ...

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Section: Cd11bsupporting

confidence: 89%

Self-renewing resident arterial macrophages arise from embryonic CX3CR1+ precursors and circulating monocytes immediately after birth

et al. 2015

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“…This would fit with our observations that CM numbers are elevated first, followed by IM. NCM numbers were not significantly elevated, which might be attributed to the longer NCM maturation time [20,21] . However, if the increased cell numbers observed in our study were caused by de novo production, monocyte maturation would have to be rapidly increased, as monocyte maturation appears to take 2 days (CM), 4 days (IM) or 7 days (NCM) under homeostatic conditions [20] .…”

Section: Differential Loss Of Monocyte Subsets From Circulation Aftermentioning

confidence: 85%

“…A labelling study in simian macaques [20] has shown that, under homeostatic conditions, CM are the first cells to be released from bone marrow, followed by IM and lastly by NCM. In humans, CM are the first cells to repopulate the bloodstream after hematopoietic stem cell transplantation [21] , making it likely that human monocytes follow a similar pattern. This would fit with our observations that CM numbers are elevated first, followed by IM.…”

Section: Differential Loss Of Monocyte Subsets From Circulation Aftermentioning

confidence: 99%

Monocyte Subsets Are Differentially Lost from the Circulation during Acute Inflammation Induced by Human Experimental Endotoxemia

et al. 2017

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Three human monocyte subsets are recognized with different functions in the immune system: CD14⁺⁺/CD16^- classical monocytes (CM), CD14⁺⁺/CD16⁺ intermediate monocytes (IM) and CD14⁺/CD16⁺⁺ non-classical monocytes (NCM). Increased IM and NCM percentages have been reported under inflammatory conditions, yet little is known about monocyte subsets at the onset of inflammation. The human endotoxemia model is uniquely capable of studying the first phases of acute inflammation induced by intravenous injection of 2 ng/kg bodyweight lipopolysaccharide (LPS) into healthy volunteers. After that, monocyte subset counts, activation/differentiation status and chemokine levels were studied over 24 h. The numbers of all subsets were decreased by >95% after LPS injection. CM numbers recovered first (3- 6 h), followed by IM (6-8 h) and NCM numbers (8-24 h). Similarly, increased monocyte counts were observed first in CM (8 h), followed by IM and NCM (24 h). Monocytes did not display a clear activated phenotype (minor increase in CD11b and CD38 expression). Plasma levels of CCL2, CCL4 and CX₃CL1 closely resembled the cell numbers of CM, IM and NCM, respectively. Our study provides critical insights into the earliest stages of acute inflammation and emphasizes the necessity to stain for different monocyte subsets when studying the role of monocytes in disease, as neither function nor kinetics of the subsets overlap.

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“…Indeed, it has been shown that LCs may originate from dermal CD14 + cells in noninflammatory settings in vitro (19). Other studies based on transcriptomic analyses have allowed reconsidering such CD14 + dermal cells as monocyte-derived macrophages most likely related to blood monocytes/macrophages rather than bona fide dermal DCs (20)(21)(22). However, whether these human monocyte-derived macrophages could differentiate into other cell types such as LCs in inflammatory conditions or at steady-state in vivo is still unclear.…”

mentioning

confidence: 99%

Functional Langerinhigh-Expressing Langerhans-like Cells Can Arise from CD14highCD16− Human Blood Monocytes in Serum-Free Condition

Picarda

Chéneau

Humbert

et al. 2016

The Journal of Immunology

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Langerhans cells (LCs) are epithelial APCs that sense danger signals and in turn trigger specific immune responses. In steady-state, they participate in the maintenance of peripheral tolerance to self-antigens whereas under inflammation LCs efficiently trigger immune responses in secondary lymphoid organs. It has been demonstrated in mice that LC-deprived epithelia are rapidly replenished by short half-life langerin-expressing monocyte-derived LCs (MDLCs). These surrogate LCs are thought to be progressively replaced by langerinhigh LCs arising from self-renewing epithelial precursors of hematopoietic origin. How LCs arise from blood monocytes is not fully understood. Hence, we sought to characterize key factors that induce differentiation of langerinhigh-expressing monocyte-derived Langerhans-like cells. We identified GM-CSF and TGF-β1 as key cytokines to generate langerinhigh-expressing cells but only in serum-free conditions. These cells were shown to express the LC-specific TROP-2 and Axl surface markers and contained Birbeck granules. Surprisingly, E-cadherin was not spontaneously expressed by these cells but required a direct contact with keratinocytes to be stably induced. MDLCs induced stronger allogeneic T cell proliferations but released low amounts of inflammatory cytokines upon TLR stimulation compared with donor-paired monocyte-derived dendritic cells. Immature langerinhigh MDLCs were responsive to MIP-3β/CCL20 and CTAC/CCL27 chemokine stimulations. Finally, we demonstrated that those cells behaved as bona fide LCs when inserted in a three-dimensional rebuilt epithelium by becoming activated upon TLR or UV light stimulations. Collectively, these results prompt us to propose these langerinhigh MDLCs as a relevant model to address LC biology–related questions.

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Human Dermal CD14 + Cells Are a Transient Population of Monocyte-Derived Macrophages

Cited by 246 publications

References 53 publications

Self-renewing resident arterial macrophages arise from embryonic CX3CR1+ precursors and circulating monocytes immediately after birth

Self-renewing resident arterial macrophages arise from embryonic CX3CR1+ precursors and circulating monocytes immediately after birth

Monocyte Subsets Are Differentially Lost from the Circulation during Acute Inflammation Induced by Human Experimental Endotoxemia

Functional Langerinhigh-Expressing Langerhans-like Cells Can Arise from CD14highCD16− Human Blood Monocytes in Serum-Free Condition

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