Macrophage: Key player in the pathogenesis of autoimmune diseases

Yang, Shuang; Zhao, Ming; Jia, Sujie

doi:10.3389/fimmu.2023.1080310

Cited by 31 publications

(15 citation statements)

References 202 publications

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“…Examples of diseases where secondary necrosis contributes to disease progression due to impaired efferocytosis include the following: In autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), impaired efferocytosis results in the buildup of apoptotic cells, leading to secondary necrosis. This release of autoantigens activates autoreactive immune cells, worsening autoimmune responses and tissue damage [110]. In atherosclerotic plaques, deficient efferocytosis causes apoptotic cell accumulation, promoting secondary necrosis and releasing pro-inflammatory molecules, exacerbating plaque instability and atherosclerosis progression [111].…”

Section: Secondary Necrosismentioning

confidence: 99%

Overnutrition and Lipotoxicity: Impaired Efferocytosis and Chronic Inflammation as Precursors to Multifaceted Disease Pathogenesis

Mann,

Sundaresan,

Shishodia

2024

Biology

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Overnutrition, driven by the consumption of high-fat, high-sugar diets, has reached epidemic proportions and poses a significant global health challenge. Prolonged overnutrition leads to the deposition of excessive lipids in adipose and non-adipose tissues, a condition known as lipotoxicity. The intricate interplay between overnutrition-induced lipotoxicity and the immune system plays a pivotal role in the pathogenesis of various diseases. This review aims to elucidate the consequences of impaired efferocytosis, caused by lipotoxicity-poisoned macrophages, leading to chronic inflammation and the subsequent development of severe infectious diseases, autoimmunity, and cancer, as well as chronic pulmonary and cardiovascular diseases. Chronic overnutrition promotes adipose tissue expansion which induces cellular stress and inflammatory responses, contributing to insulin resistance, dyslipidemia, and metabolic syndrome. Moreover, sustained exposure to lipotoxicity impairs the efferocytic capacity of macrophages, compromising their ability to efficiently engulf and remove dead cells. The unresolved chronic inflammation perpetuates a pro-inflammatory microenvironment, exacerbating tissue damage and promoting the development of various diseases. The interaction between overnutrition, lipotoxicity, and impaired efferocytosis highlights a critical pathway through which chronic inflammation emerges, facilitating the development of severe infectious diseases, autoimmunity, cancer, and chronic pulmonary and cardiovascular diseases. Understanding these intricate connections sheds light on potential therapeutic avenues to mitigate the detrimental effects of overnutrition and lipotoxicity on immune function and tissue homeostasis, thereby paving the way for novel interventions aimed at reducing the burden of these multifaceted diseases on global health.

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Section: Secondary Necrosismentioning

confidence: 99%

Overnutrition and Lipotoxicity: Impaired Efferocytosis and Chronic Inflammation as Precursors to Multifaceted Disease Pathogenesis

Mann,

Sundaresan,

Shishodia

2024

Biology

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“…24 It is known that a decrease in the basal levels of type 1 interferon (Type I IFN) and thus, a decreased release of IFN-γ by CD8 + T-cells occurs in non-obese diabetic mice. 25 T-cell activation leads to upregulation in the secretion of pro-inflammatory signatures like IFN-γ and IL-17 that cause further increase in the number of inflammatory immune cells in the vicinity of the pancreas 26,27 This leads to an increase in the accumulation of macrophages that present self-antigens to autoreactive T-cells 28,29 Parallel to a mild decrease in the number of circulating adaptive immune cells, there is an excessive pancreatic infiltration of autoreactive CD8 + cytotoxic T-cells that mediate the destruction of β-cells through the recognition of a major histocompatibility complex (MHC-I). 30 Dysregulated helper T-cells, the T h -cells or the CD4 + T-cells bring about changes in a variety of functions involving, class-switching of B-cells, maturation of T-cell subset CD8 + T-cells, and macrophage activation.…”

Section: Changes In the Adaptive Immunity Compartmentmentioning

confidence: 99%

Viral infection and host immune response in diabetes

Joshi,

Das,

Verma

et al. 2023

IUBMB Life

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Diabetes, a chronic metabolic disorder disrupting blood sugar regulation, has emerged as a prominent silent pandemic. Uncontrolled diabetes predisposes an individual to develop fatal complications like cardiovascular disorders, kidney damage, and neuropathies and aggravates the severity of treatable infections. Escalating cases of Type 1 and Type 2 diabetes correlate with a global upswing in diabetes‐linked mortality. As a growing global concern with limited preventive interventions, diabetes necessitates extensive research to mitigate its healthcare burden and assist ailing patients. An altered immune system exacerbated by chronic hyperinflammation heightens the susceptibility of diabetic individuals to microbial infections, including notable viruses like SARS‐CoV‐2, dengue, and influenza. Given such a scenario, we scrutinized the literature and compiled molecular pathways and signaling cascades related to immune compartments in diabetics that escalate the severity associated with the above‐mentioned viral infections in them as compared to healthy individuals. The pathogenesis of these viral infections that trigger diabetes compromises both innate and adaptive immune functions and pre‐existing diabetes also leads to heightened disease severity. Lastly, this review succinctly outlines available treatments for diabetics, which may hold promise as preventive or supportive measures to effectively combat these viral infections in the former.

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“…Therefore, modulation of Nur77/NR4A1 activity may hold therapeutic potential for managing these conditions. 13 The activity of Nur77/NR4A1 in macrophages is tightly regulated by various signaling pathways and co-factors. In addition to pro-inflammatory stimuli, other factors, such as Tolllike receptors (TLRs) and interferon regulatory factors (IRFs), can also influence the expression and activation of Nur77/NR4A1.…”

Section: Influence Of Nur77/nr4a1 On Macrophage Polarization Towards ...mentioning

confidence: 99%

Regulation of polarization of lung macrophages by Nur77/Nr4a1

Karikalan

Chakravarthi

2023

ACHR

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Nur77, also known as NR4A1 (nuclear receptor subfamily 4 group A member 1), is a transcription factor belonging to the NR4A subfamily of nuclear receptors. Emerging evidence suggests its involvement in modulating macrophage polarization states.Macrophages are versatile immune cells that can adopt distinct functional states depending on the signals they receive from their microenvironment. Two main polarization states are commonly recognized: the classically activated (M1) phenotype, associated with pro-inflammatory responses, and the alternatively activated (M2) phenotype, linked to tissue repair and immunoregulation. The balance between M1 and M2 polarization is critical for maintaining immune homeostasis in the lung.Several studies have indicated that Nur77/NR4A1 may influence macrophage polarization towards the M1 phenotype. Also, other studies have also indicated a potential role for Nur77 in regulating M2 polarization of macrophages. Research findings suggest a dual role for Nur77 in modulating macrophage polarization, potentially promoting both M1 and M2 phenotypes depending on the context and specific signaling cues.It's important to note that the exact mechanisms underlying Nur77's regulation of macrophage polarization in the lung are still being elucidated. Further research is needed to fully understand the complex interplay between Nur77, other transcription factors, and the signaling pathways involved in lung macrophage polarization. Nonetheless, the current evidence suggests that Nur77/NR4A1 is a key player in orchestrating the immune responses of lung macrophages and may have a role in regulating their polarization towards both M1 and M2 phenotypes.

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Macrophage: Key player in the pathogenesis of autoimmune diseases

Cited by 31 publications

References 202 publications

Overnutrition and Lipotoxicity: Impaired Efferocytosis and Chronic Inflammation as Precursors to Multifaceted Disease Pathogenesis

Overnutrition and Lipotoxicity: Impaired Efferocytosis and Chronic Inflammation as Precursors to Multifaceted Disease Pathogenesis

Viral infection and host immune response in diabetes

Regulation of polarization of lung macrophages by Nur77/Nr4a1

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