Age/autoimmunity-associated B cells in inflammatory arthritis: An emerging therapeutic target

Li, Zhenyu; Cai, Ming-Long; Qin, Yi; Chen, Zhu

doi:10.3389/fimmu.2023.1103307

Cited by 10 publications

(7 citation statements)

References 112 publications

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“…Memory B and plasma cells are pathogenic in autoimmune diseases; however, a new subset of cells—age/autoimmunity-associated B cells (ABCs)—has recently been suggested to contribute to autoimmunity ( 11 , 12 ). ABCs were initially identified as a cell population that increased with age; however, they expanded in mouse autoimmune models regardless of age.…”

Section: Introductionmentioning

confidence: 99%

“…ABCs are often variedly defined depending on the combination of these markers. Human ABC-like B cells (including CD27 – IgD – and CD11c + CD21 lo ) are more abundant in various human autoimmune diseases, such as systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) ( 11 , 12 ). However, molecules expressed in ABCs that are involved in autoimmune diseases are unknown.…”

Section: Introductionmentioning

confidence: 99%

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Upregulated Fcrl5 disrupts B cell anergy and causes autoimmune disease

Ono,

Tanaka,

Myouzen

et al. 2023

Front. Immunol.

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B cell anergy plays a critical role in maintaining self-tolerance by inhibiting autoreactive B cell activation to prevent autoimmune diseases. Here, we demonstrated that Fc receptor-like 5 (Fcrl5) upregulation contributes to autoimmune disease pathogenesis by disrupting B cell anergy. Fcrl5—a gene whose homologs are associated with human autoimmune diseases—is highly expressed in age/autoimmunity-associated B cells (ABCs), an autoreactive B cell subset. By generating B cell-specific Fcrl5 transgenic mice, we demonstrated that Fcrl5 overexpression in B cells caused systemic autoimmunity with age. Additionally, Fcrl5 upregulation in B cells exacerbated the systemic lupus erythematosus-like disease model. Furthermore, an increase in Fcrl5 expression broke B cell anergy and facilitated toll-like receptor signaling. Thus, Fcrl5 is a potential regulator of B cell-mediated autoimmunity by regulating B cell anergy. This study provides important insights into the role of Fcrl5 in breaking B cell anergy and its effect on the pathogenesis of autoimmune diseases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Upregulated Fcrl5 disrupts B cell anergy and causes autoimmune disease

Ono,

Tanaka,

Myouzen

et al. 2023

Front. Immunol.

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“…How the heterogeneity within ABC populations reported in different autoimmune and infectious diseases [38, 39] affects SjD is unknown. In SjD patients, the CD21 -/low B cells elevated in peripheral blood showed immunoglobulin gene rearrangement indicative of memory B cells and expressed antibodies reactive with nuclear and cytoplasmic autoantigens.…”

Section: Discussionmentioning

confidence: 99%

Age-associated B cell infiltration in salivary glands represents a hallmark of Sjögren’s-like disease in aging mice

Bagavant,

Durslewicz,

Pyclik

et al. 2024

Preprint

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Sjögren's disease (SjD), characterized by circulating autoantibodies and exocrine gland inflammation, is typically diagnosed in women over 50 years of age. However, the contribution of age to SjD pathogenesis is unclear. C57BL/6 female mice at different ages were studied to investigate how aging influences the dynamics of salivary gland inflammation. Salivary glands were characterized for immune cell infiltration, inflammatory gene expression, oxidative stress, and saliva production. At 8 months, gene expression of several chemokines involved in immune cell trafficking was significantly elevated. At this age, Age-associated B cells (ABCs), a unique subset of B cells expressing the myeloid markers CD11b and/or CD11c, were preferentially enriched in the salivary glands compared to other organs like the spleen or liver. The salivary gland ABCs increased with age and positively correlated with increased CD4 T follicular helper cells. By 14 months, lymphocytic foci of well-organized T and B cells spontaneously developed in the salivary glands. In addition, the mice progressively developed high titers of serum autoantibodies. A subset of aged mice developed salivary gland dysfunction mimicking SjD patients. Our data demonstrates that aging is a significant confounding factor for SjD. Thus, aged female C57BL/6 mice are more appropriate and a valuable preclinical model for investigating SjD pathogenesis and novel therapeutic interventions.

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“…RA is an autoimmune disease. It is well known that T and B lymphocytes are essential to the etiology and progression of RA [ 104 ]. Furthermore, it has been demonstrated that joint deterioration and an aggravation of clinical symptoms are associated with autoantibodies in patients with RA [ 105 , 106 ].…”

Section: Natural Productmentioning

confidence: 99%

Mechanistic role of quercetin as inhibitor for adenosine deaminase enzyme in rheumatoid arthritis: systematic review

Atta,

Salem,

El-Said

et al. 2024

Cell Mol Biol Lett

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Rheumatoid arthritis (RA) is an autoimmune disease involving T and B lymphocytes. Autoantibodies contribute to joint deterioration and worsening symptoms. Adenosine deaminase (ADA), an enzyme in purine metabolism, influences adenosine levels and joint inflammation. Inhibiting ADA could impact RA progression. Intracellular ATP breakdown generates adenosine, which increases in hypoxic and inflammatory conditions. Lymphocytes with ADA play a role in RA. Inhibiting lymphocytic ADA activity has an immune-regulatory effect. Synovial fluid levels of ADA are closely associated with the disease’s systemic activity, making it a useful parameter for evaluating joint inflammation. Flavonoids, such as quercetin (QUE), are natural substances that can inhibit ADA activity. QUE demonstrates immune-regulatory effects and restores T-cell homeostasis, making it a promising candidate for RA therapy. In this review, we will explore the impact of QUE in suppressing ADA and reducing produced the inflammation in RA, including preclinical investigations and clinical trials. Graphical Abstract

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Age/autoimmunity-associated B cells in inflammatory arthritis: An emerging therapeutic target

Cited by 10 publications

References 112 publications

Upregulated Fcrl5 disrupts B cell anergy and causes autoimmune disease

Upregulated Fcrl5 disrupts B cell anergy and causes autoimmune disease

Age-associated B cell infiltration in salivary glands represents a hallmark of Sjögren’s-like disease in aging mice

Mechanistic role of quercetin as inhibitor for adenosine deaminase enzyme in rheumatoid arthritis: systematic review

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