The HDAC10 instructs macrophage M2 program via deacetylation of STAT3 and promotes allergic airway inflammation DOI Creative Commons

Yu Zhong,

Tong Huang,

Jiewen Huang

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 13(11), P. 3568 - 3581

Published: Jan. 1, 2023

Background: Perturbation of macrophage homeostasis is one the key mechanisms airway inflammation in asthma.However, exact remain poorly understood.Objectives: We sought to examine role histone deacetylase (HDAC) 10 as an epigenetic regulator that governs M2 program and promotes asthma, elucidate underlying mechanisms.Methods: Peripheral blood biopsies were obtained from healthy individuals asthmatic patients.Asthma was induced by exposure allergen mice with myeloid-specific deletion Hdac10 (Hdac10 fl/fl -LysMCre) mice.HDAC10 inhibitor Salvianolic acid B (SAB), STAT3 selective agonist Colivelin, specific PI3K/Akt activator 1,3-Dicaffeoylquinic (DA) also used mice.For cell studies, THP1 cells, primary mouse bone marrow derived (BMDMs) related signaling pathways investigated.Results: HDAC10 expression highly expressed macrophages promoted activation patients mice.Hdac10 -LysMCre protected experimental asthma model.Hdac10 deficiency significantly attenuated decreased polarization following exposure.Mechanistically, directly binds for deacetylation macrophages, which it activates program.Importantly, we identified SAB a had protective effects against mice.Conclusions: Our results revealed HDAC10-STAT3 interaction promote implicating therapeutic target.

Language: Английский

Macrophages in health and disease DOI Creative Commons
Matthew D. Park,

Aymeric Silvin,

Florent Ginhoux

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(23), P. 4259 - 4279

Published: Nov. 1, 2022

Language: Английский

Citations

327
Tissue-specific macrophages: how they develop and choreograph tissue biology DOI Creative Commons
Elvira Mass, Falk Nimmerjahn, Katrin Kierdorf

et al.

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(9), P. 563 - 579

Published: March 15, 2023

Macrophages are innate immune cells that form a 3D network in all our tissues, where they phagocytose dying and cell debris, complexes, bacteria other waste products. Simultaneously, produce growth factors signalling molecules — such activities not only promote host protection response to invading microorganisms but also crucial for organ development homeostasis. There is mounting evidence of macrophages orchestrating fundamental physiological processes, as blood vessel formation, adipogenesis, metabolism central peripheral neuronal function. In parallel, novel methodologies have led the characterization tissue-specific macrophages, with distinct subpopulations these showing different developmental trajectories, transcriptional programmes life cycles. Here, we summarize growing knowledge macrophage diversity how subsets orchestrate tissue We further interrelate ontogeny their core functions across is, events within niche may control functionality during development, homeostasis ageing. Finally, highlight open questions will need be addressed by future studies better understand subsets. important immunity infections clearing products from maintain health regulating metabolism, many biological processes. Elvira Mass co-workers discuss populations found throughout body, highlighting shared unique aspects functions.

Language: Английский

Citations

305
Macrophages at the interface of the co-evolving cancer ecosystem DOI Creative Commons
Daan J. Kloosterman, Leila Akkari

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1627 - 1651

Published: March 15, 2023

Language: Английский

Citations

183
Immune determinants of the pre-metastatic niche DOI Creative Commons
Laura Pătraș, Lee Shaashua, Irina Matei

et al.

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 546 - 572

Published: March 1, 2023

Language: Английский

Citations

85
MultiNicheNet: a flexible framework for differential cell-cell communication analysis from multi-sample multi-condition single-cell transcriptomics data DOI Creative Commons
Robin Browaeys, Jeroen Gilis, Chananchida Sang-aram

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 14, 2023

Abstract Dysregulated cell-cell communication is a hallmark of many disease phenotypes. Due to recent advances in single-cell transcriptomics and computational approaches, it now possible study intercellular on genome- tissue-wide scale. However, most current inference tools have limitations when analyzing data from multiple samples conditions. Their main limitation that they do not address inter-sample heterogeneity adequately, which could lead false inference. This issue crucial for human cohort scRNA-seq datasets, complicating the comparison between healthy diseased subjects. Therefore, we developed MultiNicheNet ( https://github.com/saeyslab/multinichenetr ), novel framework better analyze multi-sample multi-condition data. The goals are inferring differentially expressed active ligand-receptor pairs conditions interest predicting putative downstream target genes these pairs. To achieve this goal, applies principles state-of-the-art differential expression algorithms As result, users can while adequately addressing heterogeneity, handling complex multifactorial experimental designs, correcting batch effects covariates. Moreover, uses NicheNet-v2, our new substantially improved version NicheNet’s network ligand-target prior knowledge model. We applied patient several diseases (breast cancer, squamous cell carcinoma, multisystem inflammatory syndrome children, lung fibrosis). For diseases, uncovered known aberrant signaling processes. also demonstrated MultiNicheNet’s potential perform non-trivial analysis tasks, such as studying between- within-group differences dynamics response therapy. final example, used MulitNicheNet elucidate dysregulated idiopathic pulmonary fibrosis integrated atlas Given anticipated increase datasets due technological advancements extensive atlas-building integration efforts, expect will be valuable tool uncover states.

Language: Английский

Citations

69
Mechanisms of organ fibrosis: Emerging concepts and implications for novel treatment strategies DOI
Isabella Lurje, Nadine T. Gaisa, Ralf Weiskirchen

et al.

Molecular Aspects of Medicine, Journal Year: 2023, Volume and Issue: 92, P. 101191 - 101191

Published: May 24, 2023

Language: Английский

Citations

67
Macrophage phenotypes and functions: resolving inflammation and restoring homeostasis DOI
Patricia Rodríguez-Morales, Ruth A. Franklin

Trends in Immunology, Journal Year: 2023, Volume and Issue: 44(12), P. 986 - 998

Published: Nov. 6, 2023

Language: Английский

Citations

63
CCL5-producing migratory dendritic cells guide CCR5+ monocytes into the draining lymph nodes DOI Creative Commons
Kavita Rawat, Anita Tewari, Xin Li

et al.

The Journal of Experimental Medicine, Journal Year: 2023, Volume and Issue: 220(6)

Published: March 22, 2023

Dendritic cells (DCs) and monocytes capture, transport, present antigen to cognate T in the draining lymph nodes (LNs) a CCR7-dependent manner. Since only migratory DCs express this chemokine receptor, it is unclear how reach LN. In steady-state following inhalation of several PAMPs, scRNA-seq identified LN mononuclear phagocytes as monocytes, resident, or type 1 2 conventional (c)DCs, despite downregulation Xcr1, Clec9a, H2-Ab1, Sirpa, Clec10a transcripts on cDCs. Migratory cDCs, however, upregulated Ccr7, Ccl17, Ccl22, Ccl5. expressed Ccr5, high-affinity receptor for Using two tracking methods, we observed that both CD88hiCD26lomonocytes CD88−CD26hi cDCs captured inhaled antigens lung migrated LNs. Antigen exposure mixed-chimeric Ccl5-, Ccr2-, Ccr5-, Ccr7-, Batf3-deficient mice demonstrated while antigen-bearing use CCR7 LN, CCR5 follow CCL5-secreting into where they regulate DC-mediated immunity.

Language: Английский

Citations

54
Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting DOI Creative Commons
Christina Malainou, Shifaa M Abdin, Nico Lachmann

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(19)

Published: Oct. 1, 2023

Alveolar macrophages (AMs) are the sentinel cells of alveolar space, maintaining homeostasis, fending off pathogens, and controlling lung inflammation. During acute injury, AMs orchestrate initiation resolution inflammation in order to ultimately restore homeostasis. This central role makes attractive targets for therapeutic interventions. Single-cell RNA-Seq spatial omics approaches, together with methodological advances such as generation human from pluripotent stem cells, have increased understanding ontogeny, function, plasticity during infectious sterile inflammation, which could move field closer clinical application. However, proresolution phenotypes might conflict proinflammatory antibacterial responses. Therefore, targeting at vulnerable time points over course injury harbor risk serious side effects, loss host defense capacity. Thus, identification key signaling hubs that determine functional fate decisions is utmost importance harness their potential.

Language: Английский

Citations

54
Targeting immunometabolism against acute lung injury DOI Open Access

Li Ning,

Zou Shishi,

Bo Wang

et al.

Clinical Immunology, Journal Year: 2023, Volume and Issue: 249, P. 109289 - 109289

Published: March 12, 2023

Language: Английский

Citations

42