Dietary Cows’ Milk Protein A1 Beta-Casein Increases the Incidence of T1D in NOD Mice DOI Open Access

Joanne SJ Chia,

Jennifer L. McRae,

Ashwantha Kumar Enjapoori

et al.

Nutrients, Journal Year: 2018, Volume and Issue: 10(9), P. 1291 - 1291

Published: Sept. 12, 2018

The contribution of cows' milk containing beta-casein protein A1 variant to the development type 1 diabetes (T1D) has been controversial for decades. Despite epidemiological data demonstrating a relationship between consumption and T1D incidence, direct evidence is limited. We demonstrate that early life exposure through diet can modify progression in non-obese diabetic (NOD) mice, with effect apparent later generations. Adult NOD mice from F0 generation all subsequent generations (F1 F4) were fed either or A2 supplemented diets. Diabetes incidence F0⁻F2 was similar both cohorts mice. However, doubled F3 an diet. In F4 subclinical insulitis altered glucose handling evident as 10 weeks age only. A significant decrease proportion non-conventional regulatory T cell subset defined CD4⁺CD25-FoxP3⁺ This feeding intervention study demonstrates dietary may affect homeostasis progression, although this takes manifest.

Language: Английский

Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity DOI
Shinya Tanaka, Wataru Ise, Takeshi Inoue

et al.

Nature Immunology, Journal Year: 2020, Volume and Issue: 21(8), P. 950 - 961

Published: June 22, 2020

Language: Английский

Citations

74
AIM2 deficiency in B cells ameliorates systemic lupus erythematosus by regulating Blimp-1–Bcl-6 axis-mediated B-cell differentiation DOI Creative Commons
Ming Yang, Di Long,

Longyuan Hu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Sept. 14, 2021

Abstract Absent in melanoma 2 (AIM2) has been reported to be a component of inflammasomes innate immune cells. Surprisingly, AIM2 is expressed by B cells, and higher expression observed the cells from lupus patients. To date, inflammasome-independent function remains unclear. Here, we report increased human tonsil memory germinal center (GC) plasma circulation skin lesions Conditional knockout reduces CD19 + B-cell frequency lymph nodes spleens, dampens KLH-induced IgG1-antibody production. In pristane-induced mouse model lupus, deficiency attenuates symptoms GC T follicular helper (Tfh) plasmablast Furthermore, loss leads Blimp-1 Bcl-6. However, silencing Bcl-6 no significant effect on expression, indicating that might upstream regulator for addition, IL-10 found upregulate via DNA demethylation. Together, our findings reveal highly patients promotes differentiation modulating Bcl-6–Blimp-1 axis, providing novel target SLE treatment.

Language: Английский

Citations

61
Deciphering the fibrotic process: mechanism of chronic radiation skin injury fibrosis DOI Creative Commons
Yiren Wang,

Shouying Chen,

Shuilan Bao

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 15, 2024

This review explores the mechanisms of chronic radiation-induced skin injury fibrosis, focusing on transition from acute radiation damage to a fibrotic state. It reviewed cellular and molecular responses radiation, highlighting role myofibroblasts significant impact Transforming Growth Factor-beta (TGF-β) in promoting fibroblast-to-myofibroblast transformation. The delves into epigenetic regulation gene expression, contribution extracellular matrix proteins microenvironment, immune system context fibrosis. Additionally, it discusses potential biomaterials artificial intelligence medical research advance understanding treatment suggesting future directions involving bioinformatics personalized therapeutic strategies enhance patient quality life.

Language: Английский

Citations

11
B Cells Dynamic in Aging and the Implications of Nutritional Regulation DOI Open Access
Yifei Yu, Chenxu Lu,

Weiru Yu

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(4), P. 487 - 487

Published: Feb. 8, 2024

Aging negatively affects B cell production, resulting in a decrease B-1 and B-2 cells impaired antibody responses. Age-related subsets contribute to inflammation. Investigating age-related alterations the B-cell pool developing targeted therapies are crucial for combating autoimmune diseases elderly. Additionally, optimal nutrition, including carbohydrates, amino acids, vitamins, especially lipids, play vital role supporting immune function mitigating decline activity. Research on influence of lipids shows promise improving diseases. Understanding aging considering nutritional interventions can inform strategies promoting healthy reducing disease burden.

Language: Английский

Citations

10
TLR4+CXCR4+ plasma cells drive nephritis development in systemic lupus erythematosus DOI
Kongyang Ma, Jingyi Li, Xiaohui Wang

et al.

Annals of the Rheumatic Diseases, Journal Year: 2018, Volume and Issue: 77(10), P. 1498 - 1506

Published: June 20, 2018

In patients with systemic lupus erythematosus (SLE), immune tolerance breakdown leads to autoantibody production and immune-complex glomerulonephritis. This study aimed identify pathogenic plasma cells (PC) in the development of nephritis.PC subsets peripheral blood renal tissue SLE mice were examined by flow cytometry confocal microscopy, respectively. Sorting-purified PCs from adoptively transferred into Rag2-deficient recipients, which deposition pathology investigated. culture, treated a TLR4 inhibitor for secretion enzyme-linked immunospot assay (ELISPOT). Moreover, inhibitor, followed assessment serum levels glomerulonephritis activity.The frequencies TLR4+CXCR4+ found significantly increased potent anti-dsDNA IgG, associated severe damages experimental lupus. Adoptive transfer led recipients. both showed markedly reduced IgG on blockade. vivo treatment attenuated mice.These findings demonstrate role nephritis may provide new therapeutic strategies SLE.

Language: Английский

Citations

62
Epigenetic regulation of B cells and its role in autoimmune pathogenesis DOI Creative Commons
Fan Xiao, Ke Rui, Xiaofei Shi

et al.

Cellular and Molecular Immunology, Journal Year: 2022, Volume and Issue: 19(11), P. 1215 - 1234

Published: Oct. 12, 2022

Abstract B cells play a pivotal role in the pathogenesis of autoimmune diseases. Although previous studies have shown many genetic polymorphisms associated with B-cell activation patients various disorders, progress epigenetic research has revealed new mechanisms leading to hyperactivation. Epigenetic mechanisms, including those involving histone modifications, DNA methylation, and noncoding RNAs, regulate responses, their dysregulation can contribute Patients diseases show alterations that lead initiation perpetuation inflammation. Moreover, clinical animal model promising potential therapies for patients. In this review, we present an up-to-date overview focus on roles regulating functional subsets. Furthermore, discuss highlight its contribution development Based preclinical evidence, novel biomarkers disorders.

Language: Английский

Citations

37
The IL‐21‐TET2‐AIM2‐c‐MAF pathway drives the T follicular helper cell response in lupus‐like disease DOI

Haijing Wu,

Yaxiong Deng, Di Long

et al.

Clinical and Translational Medicine, Journal Year: 2022, Volume and Issue: 12(3)

Published: March 1, 2022

Language: Английский

Citations

32
Microglial immune regulation by epigenetic reprogramming through histone H3K27 acetylation in neuroinflammation DOI Creative Commons
Minhong Huang,

Emir Malovic,

Alyssa Ealy

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 22, 2023

Epigenetic reprogramming is the ability of innate immune cells to form memories environmental stimuli (priming), allowing for heightened responses secondary stressors. Herein, we explored microglial epigenetic marks using known inflammagen LPS as a memory priming trigger and Parkinsonian-linked neurotoxic stressor manganese (Mn) trigger. To mimic physiological responses, treatment was removed by triple-washing allow cells’ acute inflammatory response reset back before applying insult. Our results show that after Mn insult, levels key proinflammatory markers, including nitrite release, iNOS mRNA protein expression, Il-6, Il-α cytokines were exaggerated in LPS-primed microglia. paradigm implies primed microglia retain can be reprogrammed augment stress. ascertain molecular underpinning this neuroimmune memory, further hypothesize contributes retention response. Interestingly, Mn-exposed, showed enhanced deposition H3K27ac H3K4me3 along with H3K4me1. We confirmed PD mouse model (MitoPark) postmortem human brains, thereby adding clinical relevance our findings. Co-treatment p300/H3K27ac inhibitor GNE-049 reduced p300 expression deposition, decreased iNOS, increased ARG1 IRF4 levels. Lastly, since mitochondrial stress driver environmentally linked Parkinson’s disease (PD) progression, examined effects on primary trigger-induced superoxide, circularity stress, membrane depolarization, suggesting beneficial consequences function. Collectively, findings demonstrate triggers shape via mark inhibiting prevent formation attenuate subsequent responses.

Language: Английский

Citations

18
Environmental Triggers of Autoreactive Responses: Induction of Antiphospholipid Antibody Formation DOI Creative Commons

Anush Martirosyan,

Rustam Aminov, Gayane Manukyan

et al.

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: July 10, 2019

Antiphospholipid antibodies (aPLs) comprise a diverse family of autoantibodies targeted against proteins with the affinity towards negatively charged phospholipids or protein-phospholipid complexes. Their clinical significance, including prothrombotic potential anti-cardiolipin (aCLs), anti-β2-glycoprotein I (aβ2-GPIs) and lupus anti-coagulant (LA), is well-established. However, ontogeny these pathogenic aPLs remains less clear. While transient appearance could be induced by various environmental factors, in genetically predisposed individuals factors may eventually lead to development antiphospholipid syndrome (APS). Since first description APS, it has been found that wide variety microbial viral agents influence production contribute manifestations APS. Many theories attempted explain different as well phenomenon termed molecular mimicry between β2-GPI molecule infection-relevant structures. In this review, we summarize critically assess non-pathogenic formation its contribution

Language: Английский

Citations

51
A comprehensive review of immune-mediated dermatopathology in systemic lupus erythematosus DOI
Qianwen Li, Haijing Wu, Wei Liao

et al.

Journal of Autoimmunity, Journal Year: 2018, Volume and Issue: 93, P. 1 - 15

Published: July 11, 2018

Language: Английский

Citations

48