B‐cell‐specific‐peroxisome proliferator‐activated receptor <i>γ</i> deficiency augments contact hypersensitivity with impaired regulatory B cells

Su, Jianbing; Wang, Keng; Zhou, Xuan; Wang, Yiyuan; Xu, Jialan; Tao, Ling; Zeng, Xiaoli; Chen, Nana; Bai, Xiaochun; Li, Xiaojuan

doi:10.1111/imm.13027

Cited by 8 publications

(6 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…mTOR also enhances the activation of PPAR-γ, a key transcription factor for adipogenesis and metabolic reprogramming in activated T cells ( 122 ). Remarkably, PPAR-γ-deficient B cells present a reduced IL-10 production and impaired suppressive capacities, while treatment with a PPAR-γ agonist significantly expanded IL-10 + B cells in high fat diet-fed mice ( 123 , 124 ). Furthermore, free fatty acid palmitate can increase survival and IL-10 synthesis by adipose tissue-resident B cells, suggesting a potential participation of lipid metabolism in Breg functions ( 125 ).…”

Section: Regulation Of Il-10 Expression By B Cellsmentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory B Cells

et al. 2021

View full text Add to dashboard Cite

Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.

show abstract

Section: Regulation Of Il-10 Expression By B Cellsmentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory B Cells

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Recent work has highlighted a significant role for Bregs in 'autoimmunity', cancers, infection, allergy and metabolic disorders [95]. Peroxisome proliferator-activated receptor gamma (PPAR-γ)-deficient B-cells show suppressed IL-10 production and suppressive ability, with PPAR-γ agonists significantly expanding IL-10 producing B-cells [96]. The knockdown of cardiolipin transacylase enzyme, tafazzin, in mesenchymal stem cells (MSC) suppresses MSC mitochondrial function, inducing a Breg phenotype in LPS-activated B-cells [97].…”

Section: B-cells Antibodies and Mitochondriamentioning

confidence: 99%

Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders

Anderson¹,

Almulla

Reíter

et al. 2023

Cells

View full text Add to dashboard Cite

Although previously restricted to a limited number of medical conditions, there is a growing appreciation that ‘autoimmune’ (or immune-mediated) processes are important aspects of a wide array of diverse medical conditions, including cancers, neurodegenerative diseases and psychiatric disorders. All of these classes of medical conditions are associated with alterations in mitochondrial function across an array of diverse cell types. Accumulating data indicate the presence of the mitochondrial melatonergic pathway in possibly all body cells, with important consequences for pathways crucial in driving CD8+ T cell and B-cell ‘autoimmune’-linked processes. Melatonin suppression coupled with the upregulation of oxidative stress suppress PTEN-induced kinase 1 (PINK1)/parkin-driven mitophagy, raising the levels of the major histocompatibility complex (MHC)-1, which underpins the chemoattraction of CD8+ T cells and the activation of antibody-producing B-cells. Many factors and processes closely associated with autoimmunity, including gut microbiome/permeability, circadian rhythms, aging, the aryl hydrocarbon receptor, brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) all interact with the mitochondrial melatonergic pathway. A number of future research directions and novel treatment implications are indicated for this wide collection of poorly conceptualized and treated medical presentations. It is proposed that the etiology of many ‘autoimmune’/‘immune-mediated’ disorders should be conceptualized as significantly determined by mitochondrial dysregulation, with alterations in the mitochondrial melatonergic pathway being an important aspect of these pathoetiologies.

show abstract

“…As shown above, Flot2 deficiency increases Beffs but not Bregs in B cells. Excessive pro-inflammatory cytokines secretion from B cells is detrimental to numerous immune diseases as it can activate T cells directly, enhanced effector B cells or impaired regulatory function in B cells can increase the T cell-IFNγ expression to aggravate inflammation and T cell-mediated diseases [31][32][33][34]. Contact hypersensitivity (CHS) is an inflammatory disease mainly mediated by T cells, and this model is also used for determining the function of B cells in vivo [35,36].…”

Section: Flot2 Deletion Promotes Ifnγ Expression Of T Cells and Exace...mentioning

confidence: 99%

Flot2 deficiency facilitates B cell‐mediated inflammatory responses and endotoxic shock

Yang,

Zhang,

Chen

et al. 2023

Immunology

View full text Add to dashboard Cite

Sepsis is a life‐threatening disease characterized by multiple organ dysfunction. B cells play a pivotal role in sepsis. Here, we first observed the significantly reduced Flot2 gene expression in B cells from patients with bacterial sepsis and endotoxin‐induced septic mice. However, the effects of Flot2 on sepsis and B‐cell immunity remain unknown. Thus, we sorted B cells from Flot2 knockout (Flot2−/−) mice, RNA‐seq revealed significantly upregulated effector B cell (Beff) cytokines such as Il6, Il1b and Cxcl10 after Flot2 deficiency, while it showed no effect on the expression of regulatory B cell (Breg) cytokines such as Il10, Tgfb. Consistently, elevated Beff cytokine IL‐6 and unchanged Breg cytokine IL‐10 were shown in B cells from Flot2−/− mice. Similar results were subsequently observed in B cell‐specific Flot2 knockout chimeric mice. Notably, Flot2 deficiency aggravated sepsis with increased lung injury and shortened survival time in vivo by facilitating Beffs but not Bregs. Taken together, our data identify Flot2 as a novel controller of B cells, Flot2 deficiency amplifies inflammation by affecting Beffs to participate in the pathogenesis and progression of sepsis.

show abstract

B‐cell‐specific‐peroxisome proliferator‐activated receptor γ deficiency augments contact hypersensitivity with impaired regulatory B cells

Cited by 8 publications

References 52 publications

Immunosuppressive Mechanisms of Regulatory B Cells

Immunosuppressive Mechanisms of Regulatory B Cells

Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders

Flot2 deficiency facilitates B cell‐mediated inflammatory responses and endotoxic shock

Contact Info

Product

Resources

About