The role of nuclear factors as “Find-Me”/alarmin signals and immunostimulation in defective efferocytosis and related disorders

Tajbakhsh, Amir; Rezaee, Mehdi; Barreto, George E.; Moallem, Seyed Adel; Henney, Neil C.; Sahebkar, Amirhossein

doi:10.1016/j.intimp.2019.106134

Cited by 21 publications

(9 citation statements)

References 166 publications

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“…Trying to understand the role of this protein in health and disease means that we have to differentiate surface activity of FHR‐1 on complement‐activating surfaces versus non‐activating surfaces. In recent reviews Tajbakhsh et al (2020) as well as Zindel and Kubes (2020) summarized how healthy, vital and apoptotic surfaces present different signals than necrotic surfaces. Once activated, C3b deposits on all surfaces and can activate the complement cascade; however, regulators either embedded in the membrane or recruited to the surface determine whether complement activation proceeds.…”

Section: Inflammatory Function Of Factor H‐related Protein 1 (Fhr‐1)mentioning

confidence: 99%

Factor H‐related protein 1: a complement regulatory protein and guardian of necrotic‐type surfaces

Skerka

Pradel

Halder

et al. 2020

British J Pharmacology

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Factor H-related protein 1 (FHR-1) is a member of the factor H protein family, which is involved in regulating innate immune complement reactions. Genetic modification of the encoding gene, CFHR1 on human chromosome 1, is involved in diseases such as age-related macular degeneration, C3glomerulopathy, and atypical hemolytic uremic syndrome, indicating an important role for FHR-1 in human health. Recent research data demonstrate that FHR-1 levels increase in IgA nephropathy and ANCA vasculitis and that FHR-1 induces strong inflammation in monocytes on necrotic-type surfaces, suggesting a complement-independent role. These new results increase our knowledge about the role of this complement protein in pathology and provide a new therapeutic target, particularly in the context of inflammatory diseases induced by necrosis. This review summarizes current knowledge about FHR-1 and discusses its role in complement reactions and inflammation. Abbreviations: FHR-1, factor H-related protein 1; IgAN, IgA associated nephropathy or Berger's disease; AMD, age-related macular degeneration; C3G complement C3 glomerulopathy; aHUS, atypical hemolytic uremic syndrome; CFH, complement factor H gene, SCR, short consensus repeat; RCA, regulator of complement activation; SLE, systemic lupus erythematosus; TCC, terminal complement complex; CRP, C-reactive protein. unclear function. Recent studies report different regulatory roles for FHR-1, both as an inhibitor of terminal complement pathway activation and as an inducer of complement by out-competing the inhibitor factor H for binding to C3b, as well as by inducing NLRP3 in monocytes. The two faces of FHR-1 suggest that the protein may act in a certain plasma concentration together with factor H to regulate complement on healthy surfaces, but that when FHR-1 concentrations increase it may also act as a deregulator and inducer of inflammation on necrotic-type surfaces. Further studies will reveal more information about the plasticity of this protein.

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Section: Inflammatory Function Of Factor H‐related Protein 1 (Fhr‐1)mentioning

confidence: 99%

Factor H‐related protein 1: a complement regulatory protein and guardian of necrotic‐type surfaces

Skerka

Pradel

Halder

et al. 2020

British J Pharmacology

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“…Failure in the process of efferocytosis is not only associated with the development of SLE (Abdolmaleki et al, 2018; Boada‐Romero et al, 2020; Tajbakhsh et al, 2020) and related, or SLE‐like disorders (Boada‐Romero et al, 2020; Tajbakhsh et al, 2020), but also with other autoimmune diseases such as rheumatoid arthritis, type I diabetes, multiple sclerosis, autoimmune lymphoproliferative syndrome, ulcerative colitis, Crohn's diseases, and autoimmune uveitis (reviewed in Abdolmaleki et al, 2018; Boada‐Romero et al, 2020). In this regard, it is obviously possible to continue the above list of diseases by including JSLE, which is also characterized by increased apoptosis rates (Midgley et al, 2009), aside from JIA or KD in which the processes related to the formation or removal of apoptotic bodies have not been well studied yet and possibly due to the lack of obvious involvement in the pathogenesis of these diseases.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil cytosolic factor 2 (NCF2) gene polymorphism is associated with juvenile‐onset systemic lupus erythematosus, but probably not with other autoimmune rheumatic diseases in children

Bakutenko

Haurylchyk

Nikitchenko

et al. 2021

Molec Gen & Gen Med

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Background Genetic variations of neutrophil cytosolic factor 2 (NCF2), a subunit of NADPH oxidase, are usually associated with chronic granulomatous disease, and their relationship with autoimmune disorders through the defective NADPH oxidase function during phagocytosis is suggested. Our study aimed to explore whether there is an association between the non‐synonymous single nucleotide polymorphism in the NCF2 gene (rs17849502, NC_000001.11:g.183563445G>T) and the development of juvenile autoimmune rheumatic diseases. Methods In order to test this hypothesis, we conducted a pilot case–control study. In total, 709 children and adolescents, all Belarusians, were involved in the study including patients with juvenile‐onset systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), Kawasaki disease (KD), and subjects without autoimmune and inflammatory diseases as the clinical control, as well as health newborns as the population control. Real‐time polymerase chain reaction was used for genotyping. Results The minor T allele of NCF2 occurred most frequently in patients with JSLE (OR = 2.60, 95% CI = 1.18–5.73, p = 0.023 as compared to the clinical control). In groups with JIA and KD, its frequency did not differ from the control. The TT genotype was only observed in 5.7% of patients with JSLE (p = 0.007), but not in other groups. Conclusion Therefore, our study suggested that NCF2 rs17849502 polymorphism is a potential genetic risk factor for JSLE, while it is probably not for such autoimmune rheumatic diseases as JIA or KD.

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“…Mechanically, apoptotic cells are eliminated by M2-like macrophages in a normally non-inflammatory response named efferocytosis (49). Such response gives rise to an increase of anti-inflammatory cytokines and a reduction of pro-inflammatory cytokines (50). Therefore, the inflammation in LN could be caused by nonfunctional M2-like macrophages, which have lost their anti-inflammatory property.…”

Section: M2-like Macrophages In Slementioning

confidence: 99%

Macrophage Polarization and Plasticity in Systemic Lupus Erythematosus

Ahamada

Jia

2021

Front. Immunol.

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Systemic lupus erythematosus (SLE) is an autoimmune disease that attacks almost every organ. The condition mostly happens to adults but is also found in children, and the latter have the most severe manifestations. Among adults, females, especially non-Caucasian, are mostly affected. Even if the etiology of SLE remains unclear, studies show a close relation between this disease and both genetics and environment. Despite the large number of published articles about SLE, we still do not have a clear picture of its pathogenesis, and no specific drug has been found to treat this condition effectively. The implication of macrophages in SLE development is gaining ground, and studying it could answer these gaps. Indeed, both in vivo and in vitro studies increasingly report a strong link between this disease and macrophages. Hence, this review aims to explore the role of macrophages polarization and plasticity in SLE development. Understanding this role is of paramount importance because in-depth knowledge of the connection between macrophages and this systemic disease could clarify its pathogenesis and provide a foundation for macrophage-centered therapeutic approaches.

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The role of nuclear factors as “Find-Me”/alarmin signals and immunostimulation in defective efferocytosis and related disorders

Cited by 21 publications

References 166 publications

Factor H‐related protein 1: a complement regulatory protein and guardian of necrotic‐type surfaces

Factor H‐related protein 1: a complement regulatory protein and guardian of necrotic‐type surfaces

Neutrophil cytosolic factor 2 (NCF2) gene polymorphism is associated with juvenile‐onset systemic lupus erythematosus, but probably not with other autoimmune rheumatic diseases in children

Macrophage Polarization and Plasticity in Systemic Lupus Erythematosus

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