Immunopathogenesis of Ocular Behçet’s Disease

Abstract

Behçet's disease (BD) is a chronic recurrent systemic inflammatory disorder of unknown etiology characterized by oral and genital ulcerations, skin lesions, and uveitis. The ocular involvement of BD, or Behçet's uveitis (BU), is characterized by panuveitis or posterior uveitis with occlusive retinal vasculitis and tends to be more recurrent and sight threatening than other endogenous autoimmune uveitides, despite aggressive immunosuppression. Although pathogenesis of BD is unclear, researches have revealed that immunological aberrations may be the cornerstone of BD development. General hypothesis of BD pathogenesis is that inflammatory response is initiated by infectious agents or autoantigens in patients with predisposing genetic factors and perpetuated by both innate and acquired immunity. In addition, a network of immune mediators plays a substantial role in the inflammatory cascade. Recently, we found that the immunopathogenesis of BU is distinct from other autoimmune uveitides regarding intraocular effector cell profiles, maturation markers of dendritic cells, and the cytokine/chemokine environment. In addition, accumulating evidence indicates the involvement of Th17 cells in BD and BU. Recent studies on genetics and biologics therapies in refractory BU also support the immunological association with the pathogenesis of BU. In this review, we provide an overview of novel findings regarding the immunopathogenesis of BU.

Interleukin 18, soluble cluster of differentiation 40, platelet factor 4 variant 1, and neutrophil gelatinase-associated lipocalin can be used as biomarkers to aid activity and diagnosis in ocular Behçet’s disease

“…The source of the IL-18 increases reported here may be monocyte and macrophage cells activated due to BD. This is because in ammation is one of the main symptoms in BD, and in this case, it has been reported that monocytes and macrophages produce a series of pro-in ammatory cytokines [6, 40,41]. It has been previously reported that the amount of circulating IL-18 increases during BD regardless of ocular manifestation [10].…”

Interleukin 18, soluble cluster of differentiation 40, platelet factor 4 variant 1, and neutrophil gelatinase-associated lipocalin can be used as biomarkers to aid activity and diagnosis in ocular Behçet’s disease

“…The source of the IL-18 increases reported here may be monocyte and macrophage cells activated due to BD. This is because in ammation is one of the main symptoms in BD, and in this case, it has been reported that monocytes and macrophages produce a series of pro-in ammatory cytokines [6, 40,41]. It has been previously reported that the amount of circulating IL-18 increases during BD regardless of ocular manifestation [10].…”

Functional and taxonomic dysbiosis of the supragingival plaque metagenome in Behçet’s disease

“…The microbiome analysis in BD patients have previously been studied in various population including Turkish, British, Mongolian, and Dutch population [ 22–25 ]. Although those studies have identified microorganisms from salivary sample of BD patients, there is no conclusive evidence of these microorganisms linking directly to the disease [ 36 ]. The present study investigated the oral microbial composition in dental plaque of BD patients in a Thai population, using shotgun metagenomic analysis.…”

Integrative Multi-omics and Network Pharmacology Reveal the Mechanisms of Xiaoyaosan in Treating Depression

“…Studies have confirmed that mTOR inhibitors can block the differentiation of CD4+ T cells into Th17 cells and promote the generation of Treg cells. MTOR inhibitors communicate through the PI3K/Akt/mTOR pathway, which promotes the expression of Treg genes while inhibiting the differentiation of Th17, leading to a shift in the balance of Treg/Th17 toward immune tolerance and the direction of Tregs. Research has shown that the PI3K/Akt/mTOR signaling pathway has a positive regulatory effect on Th17 cells.…”

Interleukin 18, soluble cluster of differentiation 40, platelet factor 4 variant 1, and neutrophil gelatinase-associated lipocalin can be used as biomarkers to aid activity and diagnosis in ocular Behçet’s disease

“…The source of the IL-18 increases reported here may be monocyte and macrophage cells activated due to BD. This is because in ammation is one of the main symptoms in BD, and in this case, it has been reported that monocytes and macrophages produce a series of pro-in ammatory cytokines [6, 40,41]. It has been previously reported that the amount of circulating IL-18 increases during BD regardless of ocular manifestation [10].…”

Functional and taxonomic dysbiosis of the supragingival plaque metagenome in Behçet’s disease

“…The microbiome analysis in BD patients have previously been studied in various population including Turkish, British, Mongolian, and Dutch population [ 22–25 ]. Although those studies have identified microorganisms from salivary sample of BD patients, there is no conclusive evidence of these microorganisms linking directly to the disease [ 36 ]. The present study investigated the oral microbial composition in dental plaque of BD patients in a Thai population, using shotgun metagenomic analysis.…”

Integrative Multi-omics and Network Pharmacology Reveal the Mechanisms of Xiaoyaosan in Treating Depression

“…Studies have confirmed that mTOR inhibitors can block the differentiation of CD4+ T cells into Th17 cells and promote the generation of Treg cells. MTOR inhibitors communicate through the PI3K/Akt/mTOR pathway, which promotes the expression of Treg genes while inhibiting the differentiation of Th17, leading to a shift in the balance of Treg/Th17 toward immune tolerance and the direction of Tregs. Research has shown that the PI3K/Akt/mTOR signaling pathway has a positive regulatory effect on Th17 cells.…”

Interleukin 18, soluble cluster of differentiation 40, platelet factor 4 variant 1, and neutrophil gelatinase-associated lipocalin can be used as biomarkers to aid activity and diagnosis in ocular Behçet’s disease

“…The source of the IL-18 increases reported here may be monocyte and macrophage cells activated due to BD. This is because in ammation is one of the main symptoms in BD, and in this case, it has been reported that monocytes and macrophages produce a series of pro-in ammatory cytokines [6, 40,41]. It has been previously reported that the amount of circulating IL-18 increases during BD regardless of ocular manifestation [10].…”

Functional and taxonomic dysbiosis of the supragingival plaque metagenome in Behçet’s disease

“…The microbiome analysis in BD patients have previously been studied in various population including Turkish, British, Mongolian, and Dutch population [ 22–25 ]. Although those studies have identified microorganisms from salivary sample of BD patients, there is no conclusive evidence of these microorganisms linking directly to the disease [ 36 ]. The present study investigated the oral microbial composition in dental plaque of BD patients in a Thai population, using shotgun metagenomic analysis.…”

Integrative Multi-omics and Network Pharmacology Reveal the Mechanisms of Xiaoyaosan in Treating Depression

“…Studies have confirmed that mTOR inhibitors can block the differentiation of CD4+ T cells into Th17 cells and promote the generation of Treg cells. MTOR inhibitors communicate through the PI3K/Akt/mTOR pathway, which promotes the expression of Treg genes while inhibiting the differentiation of Th17, leading to a shift in the balance of Treg/Th17 toward immune tolerance and the direction of Tregs. Research has shown that the PI3K/Akt/mTOR signaling pathway has a positive regulatory effect on Th17 cells.…”