Distinct macrophage phenotypes skewed by local granulocyte macrophage colony‐stimulating factor (GM‐CSF) and macrophage colony‐stimulating factor (M‐CSF) are associated with tissue destruction and intimal hyperplasia in giant cell arteritis

Jiemy, William F.; Sleen, Yannick van; Geest, Kornelis S M van der; Berge, Hilde Anna ten; Abdulahad, Wayel H.; Sandovici, Maria; Boots, Annemieke M. H.; Heeringa, Peter; Brouwer, Elisabeth

doi:10.1002/cti2.1164

Cited by 47 publications

(50 citation statements)

References 44 publications

(91 reference statements)

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“…However, the precise cellular source of the circulating VEGF in GCA patients has not been determined. A close correlation between tissue site and macrophage functional commitment in the vasculitic lesions has recently been confirmed by Jiemy et al, who showed that MMP-9 + macrophages were placed at areas of tissue destruction, while FRβ+ macrophages were positioned in the hyperplastic intima ( 27 ).…”

Section: Innate Immunity In Gcamentioning

confidence: 70%

Innate and Adaptive Immunity in Giant Cell Arteritis

et al. 2021

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Autoimmune diseases can afflict every organ system, including blood vessels that are critically important for host survival. The most frequent autoimmune vasculitis is giant cell arteritis (GCA), which causes aggressive wall inflammation in medium and large arteries and results in vaso-occlusive wall remodeling. GCA shares with other autoimmune diseases that it occurs in genetically predisposed individuals, that females are at higher risk, and that environmental triggers are suspected to beget the loss of immunological tolerance. GCA has features that distinguish it from other autoimmune diseases and predict the need for tailored diagnostic and therapeutic approaches. At the core of GCA pathology are CD4+ T cells that gain access to the protected tissue niche of the vessel wall, differentiate into cytokine producers, attain tissue residency, and enforce macrophages differentiation into tissue-destructive effector cells. Several signaling pathways have been implicated in initiating and sustaining pathogenic CD4+ T cell function, including the NOTCH1-Jagged1 pathway, the CD28 co-stimulatory pathway, the PD-1/PD-L1 co-inhibitory pathway, and the JAK/STAT signaling pathway. Inadequacy of mechanisms that normally dampen immune responses, such as defective expression of the PD-L1 ligand and malfunction of immunosuppressive CD8+ T regulatory cells are a common theme in GCA immunopathology. Recent studies are providing a string of novel mechanisms that will permit more precise pathogenic modeling and therapeutic targeting in GCA and will fundamentally inform how abnormal immune responses in blood vessels lead to disease.

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Section: Innate Immunity In Gcamentioning

confidence: 70%

Innate and Adaptive Immunity in Giant Cell Arteritis

et al. 2021

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“…Further evidence indicates that the non-classical monocyte subset is the main source of MMP-9 and associated enzymes, in addition to pro-angiogenic factors such as YKL-40 [35,42,43]. Moreover, (classical) monocytes of GCA patients show upregulated CD64 expression but lowered expression of folate receptor β, which is likely a sign of an activated phenotype [41,44].…”

Section: Monocytes In Gcamentioning

confidence: 99%

“…In contrast to CD206+/MMP-9+/YKL-40+ macrophages, FRβ+ macrophages were mainly found in the adventitia and inner-intima, adjacent to CD206+MMP-9+ macrophages [44,61]. FRβ+ macrophages are likely skewed by local M-CSF signals as opposed to GM-CSF signals that have been reported to diminish FRβ expression by macrophages [55,56].…”

Section: Macrophage Heterogeneity and Their Roles In The Vasculopathy Of Gcamentioning

confidence: 99%

“…Besides citrate, succinate accumulation in activated macrophages results in HIF-1α activation that induces inflammatory mediators such as IL-1β [77]. IL-1β has been described as one of the important factors contributing to the pathogenesis of GCA [44,78]. The regulation of IL-1β via metabolic reprogramming in macrophages points to a possibility of metabolic activation via HIF-1α in GCA.…”

Section: Macrophage Metabolism In Gcamentioning

confidence: 99%

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Functionally Heterogenous Macrophage Subsets in the Pathogenesis of Giant Cell Arteritis: Novel Targets for Disease Monitoring and Treatment

Esen

Jiemy

Sleen

et al. 2021

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Giant cell arteritis (GCA) is a granulomatous large-vessel vasculitis that affects adults above 50 years of age. In GCA, circulating monocytes are recruited to the inflamed arteries. With cues from the vascular microenvironment, they differentiate into macrophages and play important roles in the pathogenesis of GCA via pro-inflammatory cytokine production and vascular remodeling. However, a deeper understanding of macrophage heterogeneity in GCA pathogenesis is needed to assist the development of novel diagnostic tools and targeted therapies. Here, we review the current knowledge on macrophage heterogeneity and diverse functions of macrophage subsets in the pathogenesis of GCA. We next discuss the possibility to exploit their heterogeneity as a source of novel biomarkers and as targets for nuclear imaging. Finally, we discuss novel macrophage-targeted therapies and future directions for targeting these cells in GCA.

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“…The formation of new vessels is a complex process involving many types of cells including macrophages. In fact, the overexpression of colony stimulating factor 1 (CSF-1), in a mouse model, resulted in a premature accumulation of macrophages in the hyperplastic lesion, an early angiogenic switch and consequently accelerated the transition to malignancy ( 79 ).…”

Section: The Role Of Angiogenesis In Allmentioning

confidence: 99%

The Complexity of the Tumor Microenvironment and Its Role in Acute Lymphoblastic Leukemia: Implications for Therapies

et al. 2021

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The microenvironment that surrounds a tumor, in addition to the tumor itself, plays an important role in the onset of resistance to molecularly targeted therapies. Cancer cells and their microenvironment interact closely between them by means of a molecular communication that mutually influences their biological characteristics and behavior. Leukemia cells regulate the recruitment, activation and program of the cells of the surrounding microenvironment, including those of the immune system. Studies on the interactions between the bone marrow (BM) microenvironment and Acute Lymphoblastic Leukemia (ALL) cells have opened a scenario of potential therapeutic targets which include cytokines and their receptors, signal transduction networks, and hypoxia-related proteins. Hypoxia also enhances the formation of new blood vessels, and several studies show how angiogenesis could have a key role in the pathogenesis of ALL. Knowledge of the molecular mechanisms underlying tumor-microenvironment communication and angiogenesis could contribute to the early diagnosis of leukemia and to personalized molecular therapies. This article is part of a Special Issue entitled: Innovative Multi-Disciplinary Approaches for Precision Studies in Leukemia edited by Sandra Marmiroli (University of Modena and Reggio Emilia, Modena, Italy) and Xu Huang (University of Glasgow, Glasgow, United Kingdom).

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Distinct macrophage phenotypes skewed by local granulocyte macrophage colony‐stimulating factor (GM‐CSF) and macrophage colony‐stimulating factor (M‐CSF) are associated with tissue destruction and intimal hyperplasia in giant cell arteritis

Cited by 47 publications

References 44 publications

Innate and Adaptive Immunity in Giant Cell Arteritis

Innate and Adaptive Immunity in Giant Cell Arteritis

Functionally Heterogenous Macrophage Subsets in the Pathogenesis of Giant Cell Arteritis: Novel Targets for Disease Monitoring and Treatment

The Complexity of the Tumor Microenvironment and Its Role in Acute Lymphoblastic Leukemia: Implications for Therapies

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