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Inducible costimulator ligand (ICOSL) on CD19⁺ B cells is involved in immunopathological damage of rheumatoid arthritis (RA).

ABSTRACT: Inducible costimulator (ICOS) and its ligand (ICOSL) are critical to regulate the immune response in autoimmune diseases. The participation of B lymphocytes exhibits pathogenic potential in the disease process of rheumatoid arthritis (RA). However, the precise role of ICOSL in RA remains unclear. In this study, we aimed to explore the regulatory effects of CD19⁺ICOSL⁺ B cells in the pathogenesis of RA. We demonstrated the increased expression of ICOS and ICOSL in patients with RA and collagen-induced arthritis (CIA) mice. The population of CD19⁺ICOSL⁺ B-cell subset was significantly correlated with clinicopathological characteristics of RA patients and CIA mice. Adoptive transfer of CD19⁺ICOSL⁺ B cells aggravated arthritic progression in CIA mice. Moreover, microarray analysis revealed that CD19⁺ICOSL⁺ cells could exert pivotal effect in pathological process of RA. Further blocking of ICOSL significantly inhibited proinflammatory responses and ameliorated arthritic progression. Therefore, CD19⁺ICOSL⁺ B-cell subset could be defined as a specific pathogenic cell subpopulation involved in immunopathological damage of RA. Blockade of ICOSL is promising to be a potential new approach for RA therapy.

SUBMITTER: Ding S

PROVIDER: S-EPMC9666393 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Inducible costimulator ligand (ICOSL) on CD19+ B cells is involved in immunopathological damage of rheumatoid arthritis (RA).

Ding Sisi S Sun Zhiyong Z Jiang Juean J Chang Xin X Shen Yu Y Gu Yanzheng Y Liu Cuiping C

Frontiers in immunology 20221102

Inducible costimulator (ICOS) and its ligand (ICOSL) are critical to regulate the immune response in autoimmune diseases. The participation of B lymphocytes exhibits pathogenic potential in the disease process of rheumatoid arthritis (RA). However, the precise role of ICOSL in RA remains unclear. In this study, we aimed to explore the regulatory effects of CD19+ICOSL+ B cells in the pathogenesis of RA. We demonstrated the increased expression of ICOS and ICOSL in patients w ...[more]

PMID: 36405702

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Project description:BackgroundIt has been shown that certain severe and refractory asthma cases are caused by neutrophil and not eosinophil infiltration. Inducible costimulatory molecular ligand (ICOSL) expression is closely associated with tumor and autoimmune diseases, yet a limited amount of data has been published regarding the significance of ICOSL in children with neutrophilic asthma. The present study aimed to explore the clinical significance of abnormal expression of ICOSL in peripheral blood and bronchoalveolar lavage fluid (BALF) samples of children with neutrophilic asthma.MethodsSelected children from the Children's Hospital of Soochow University who met the diagnostic criteria of asthma and excluded patients with a pathogen-positive etiology. Children who were admitted to the hospital for foreign body inhalation in the same period acted as the control group. Children with more than 50% of neutrophils in BALF samples were assigned to the neutrophilic asthma group (NA group), and the remaining subjects composed the asthma group (A group). The expression levels of ICOSL, IL-4, IL-17, IFN-γ, neutrophil elastase (NE), and matrix metalloproteinase-9 (MMP-9) were detected in plasma and BALF samples by enzyme-linked immunosorbent assays, in order to analyze the differences in the levels of cytokines and clinical characteristics between children with neutrophilic asthma and non-neutrophilic asthma. Moreover, the potential mechanism of ICOSL in neutrophilic asthma was explored.Results32 children were enrolled: 12 children in the NA group and 20 children in the A group. The mean hospitalization time of the NA group was longer than that of the A group (P<0.05). The concentration levels of ICOSL, IL-17, NE, and MMP-9 in plasma and BALF samples in the NA group were higher than those in the A group, while the levels of IFN-γ exhibited opposite. A significant correlation was found between ICOSL and IL-17 levels in plasma (r=0.753, P=0.012) and BALF (r=0.774, P=0.009) samples in the NA group.ConclusionsChildren with neutrophilic asthma were more severely affected, experiencing a considerably more difficult clinical treatment and longer hospitalization time. ICOSL may regulate the secretion of IL-17 by Th17 and increase the levels of NE and MMP-9, which are involved in the development of immune inflammation in neutrophils.

Dataset Information

Inducible costimulator ligand (ICOSL) on CD19⁺ B cells is involved in immunopathological damage of rheumatoid arthritis (RA).

Publications

Inducible costimulator ligand (ICOSL) on CD19<sup>+</sup> B cells is involved in immunopathological damage of rheumatoid arthritis (RA).

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