Fate mapping of peripherally derived macrophages reveals a long-lasting engrafted population that maintains a distinct transcriptomic profile for up to 8 months after Traumatic Brain Injury DOI Open Access
Maria Serena Paladini, Benjamin A. Yang, Xi Feng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Abstract Traumatic Brain Injury (TBI) is one of the most established environmental risk factors for development dementia and long term neurological deficits representing a critical health problem our society. It well-established that TBI-induced neuroinflammation contributes to long-lasting cognitive engages brain-resident macrophages (microglia) as well monocytes-derived (MDMs) recruited from periphery. While numerous studies have characterized microglia response TBI, role early infiltrated MDMs in dysfunctions, fate TBI remains unknown. Microglia distinct embryological origins it unclear if can fully transition after infiltrating brain. This gap knowledge due fact brain engraftment, stop expressing their signature markers, thus making discrimination resident cells elusive. Here, first time, we longitudinally trace by taking advantage two complementary yet mapping mouse lines, CCR2-creER T2 Ms4a3-cre, where inflammatory monocytes are permanently labeled even situ reprogramming. We demonstrated persist up 8 months adult female male mice. Notably, retain phagocytic activity while remaining transcriptomically microglia, show associated with aging disease. Our data significantly advance understanding provide developing more targeted therapeutic interventions myeloid cells.

Language: Английский

Clonal hematopoiesis-associated motoric deficits caused by monocyte-derived microglia accumulating in aging mice DOI Creative Commons
Jung‐Seok Kim, Sébastien Trzebanski, Sun‐Hye Shin

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(5), P. 115609 - 115609

Published: April 24, 2025

Language: Английский

Citations

0
Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumors DOI
Samarth Hegde, Bruno Giotti, Brian Y. Soong

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 28, 2024

Monocyte-derived macrophages (mo-macs) drive immunosuppression in the tumor microenvironment (TME) and tumor-enhanced myelopoiesis bone marrow (BM) fuels these populations. Here, we performed paired transcriptome chromatin analysis over continuum of BM myeloid progenitors, circulating monocytes, tumor-infiltrating mo-macs mice patients with lung cancer to identify progenitor programs that fuel pro-tumorigenic mo-macs. Analyzing accessibility histone mark changes, show tumors prime for Nfe2l2 (NRF2) progenitors as a cytoprotective response oxidative stress. NRF2 activity is sustained increased during monocyte differentiation into TME regulate stress, turn promoting metabolic adaptation, resistance cell death, contributing immunosuppressive phenotype. genetic deletion pharmacological inhibition significantly reduced mo-macs' survival TME, enabling NK T therapeutic antitumor immunity synergizing checkpoint blockade strategies. Altogether, our study identifies targetable epigenetic node dysregulation sustains immunoregulatory TME.

Language: Английский

Citations

3
Innate players in Th2 and non-Th2 asthma - emerging roles for the epithelial cell, mast cell and monocyte/macrophage network DOI
Johanna Kotrba,

Ilka Müller,

Alexander Pausder

et al.

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 327(6), P. C1373 - C1383

Published: Oct. 14, 2024

Asthma is one of the most common chronic respiratory diseases and characterized by airway inflammation, increased mucus production, structural changes in airways. Recently, there increasing evidence that disease much more heterogeneous than expected, with several distinct asthma endotypes. Based on specificity T cells as best-known driving force bronchial categorized into helper cell 2 (Th2) non-Th2 asthma. The studied effector Th2 include eosinophils. In contrast to asthma, less known about pathophysiology which often associated treatment resistance. Besides cells, interaction myeloid such monocytes/macrophages mast epithelium significantly contributes pathogenesis However, underlying molecular regulation particularly specific relevance this cellular network certain endotypes remain be understood. review, we summarize recent findings complex interplay between epithelial “nonclassical” innate ultimate goal providing rationale for future research targeted therapy regimens.

Language: Английский

Citations

3
Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity DOI
Anna Appios, James Davies, Sofía Sirvent

et al.

Science Immunology, Journal Year: 2024, Volume and Issue: 9(99)

Published: Sept. 6, 2024

Langerhans cells (LCs) are distinct among phagocytes, functioning both as embryo-derived, tissue-resident macrophages in skin innervation and repair migrating professional antigen-presenting cells, a function classically assigned to dendritic (DCs). Here, we demonstrate that intrinsic extrinsic factors imprint this dual identity. Using ablation of embryo-derived LCs the murine adult tracking differentiation incoming monocyte-derived replacements, found intraepidermal heterogeneity. We observed ontogenically monocytes give rise LCs. Within epidermis, Jagged-dependent activation Notch signaling, likely within hair follicle niche, provided an initial site LC commitment before metabolic adaptation survival In human skin, newborns retained transcriptional evidence their macrophage origin, but was superseded by DC-like immune modules after postnatal expansion. Thus, niches replicates conditioning at birth, permitting network.

Language: Английский

Citations

1
Never trust a single myeloid marker: Ly6G on repair-promoting lung macrophages DOI
Chrysante S. Iliakis, Andreas Wack

Science Immunology, Journal Year: 2024, Volume and Issue: 9(98)

Published: Aug. 2, 2024

Short-lived repair-promoting macrophages are recruited to foci of lung damage during influenza infection—and they Ly6G positive (see related Research Article by Ruscitti et al. ).

Language: Английский

Citations

0
Unveiling a unique macrophage population in exocrine glands sustained by ILC2-derived GM-CSF DOI Open Access
Frederike Westermann, Selma Tuzlak, Victor Kreiner

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 3, 2024

Summary Granulocyte-macrophage colony-stimulating factor (GM-CSF) has a non-redundant role in the emergence and maintenance of alveolar macrophages (AMs). However, its developmental steady-state myelopoiesis outside lung is largely unexplored. Scanning through developing tissues using Fate-map reporter GM-CSF mouse strain, we discovered that was produced by type 2 innate lymphoid cells (ILC2s) submandibular sublingual salivary gland (SG) during postnatal development. producing ILC2s foster development hitherto undescribed phagocyte subset, which named adenophages. Detailed analysis focusing on phenotypic transcriptional profiling revealed adenophages display shared aspects both, dendritic (DCs). We found them to be homogenously distributed across SG, but always close proximity myoepithelial cells. Importantly, were present throughout all analyzed exocrine glands such as lacrimal mammary glands, also identified human SG sections, indicating conserved species.

Language: Английский

Citations

0
Inflammation-associated monocytes express ACOD1 to curtail inflammatory behaviour in IBD and experimental colitis DOI Open Access
Gareth‐Rhys Jones,

Broc Drury,

T Alegbe

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 15, 2024

Abstract Monocytes are essential for replenishing homeostatic macrophages in the intestine. However, they also accumulate significant numbers when intestinal homeostasis is disrupted diseases, such as inflammatory bowel disease (IBD). The molecular pathways governing monocyte behaviour across these different contexts remain poorly understood. Here, we profile / macrophage compartment human IBD using single-cell RNA sequencing and identify a discrete population of monocytes that IBD, which term inflammation associated (IAMs). These can be identified by expression CD319, CD274 CCRL2, demonstrate increased susceptibility genes. By performing cross-species analysis, show an analogous IAMs during chemically induced colitis mice. Using transgenic fate mapping approaches, cells likely derive from precursor bone marrow (BM) locally imprinted to produce heightened IL-1β TNF mouse humans. Importantly, co-incident with hyper-inflammatory phenotype, same uniquely specifically express aconitate decarboxylase (ACOD1) response local Toll-like receptor (TLR) interferon (IFN) signalling, limit unrestricted cytokine production. Thus, environment after injury instructs both recovery within transitioning absent health.

Language: Английский

Citations

0
Fate mapping of peripherally derived macrophages reveals a long-lasting engrafted population that maintains a distinct transcriptomic profile for up to 8 months after Traumatic Brain Injury DOI Open Access
Maria Serena Paladini, Benjamin A. Yang, Xi Feng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Abstract Traumatic Brain Injury (TBI) is one of the most established environmental risk factors for development dementia and long term neurological deficits representing a critical health problem our society. It well-established that TBI-induced neuroinflammation contributes to long-lasting cognitive engages brain-resident macrophages (microglia) as well monocytes-derived (MDMs) recruited from periphery. While numerous studies have characterized microglia response TBI, role early infiltrated MDMs in dysfunctions, fate TBI remains unknown. Microglia distinct embryological origins it unclear if can fully transition after infiltrating brain. This gap knowledge due fact brain engraftment, stop expressing their signature markers, thus making discrimination resident cells elusive. Here, first time, we longitudinally trace by taking advantage two complementary yet mapping mouse lines, CCR2-creER T2 Ms4a3-cre, where inflammatory monocytes are permanently labeled even situ reprogramming. We demonstrated persist up 8 months adult female male mice. Notably, retain phagocytic activity while remaining transcriptomically microglia, show associated with aging disease. Our data significantly advance understanding provide developing more targeted therapeutic interventions myeloid cells.

Language: Английский

Citations

0