Crucial role of OX40/OX40L signaling in a murine model of asthma

Lei, Wei; Zeng, Daxiong; Liu, Gaoqin; Zhu, Yehan; Wang, Jiajia; Wu, Hongya; Jiang, Jian‐Hua; Huang, Jianan

doi:10.3892/mmr.2018.8453

Cited by 8 publications

(5 citation statements)

References 61 publications

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“…This was further supported by Farres et al, who showed that increased expression of OX40L on B cells is associated with the level of total IgE in allergic asthma patients ( 19 ). These findings are in line with murine asthma models, in which OX40L is highly expressed by a variety of cells within the lung during an induced allergic reaction ( 20 , 21 ). Although, in general, decreased serum levels were observed in AD, adults with concomitant asthma had the highest levels of serum sOX40.…”

Section: Discussionsupporting

confidence: 83%

The OX40 Axis is Associated with Both Systemic and Local Involvement in Atopic Dermatitis

Elsner¹,

Carlsson²,

Stougaard³

et al. 2020

Acta Derm Venerol

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Atopic dermatitis is a chronic, or chronically relapsing, inflammatory skin disease dominated by Th2 cells. The costimulatory T-cell receptor OX40 and its ligand, OX40L, are crucial for the generation of Th2 memory cells, and may thus play a central role in the pathogenesis and chronicity of atopic dermatitis. This study shows that OX40 expression is increased on skin-homing T cells in patients with atopic dermatitis, and that OX40 and OX40L cells are colocalized in the skin. These findings indicate that the OX40 system could play a pivotal role in the inflammatory reaction of atopic dermatitis in the skin.Atopic dermatitis (AD) is a chronic, or chronically relapsing, inflammatory skin disease associated with asthma and allergic rhinitis, and is dominated by Th2 cells. The co-stimulatory T-cell receptor OX40 and its ligand, OX40L, play a central role in the pathogenesis of AD, as their interactions are crucial for the generation of T H 2 memory cells. Using enzyme-linked immunoassay (ELISA) and flow cytometry on blood samples from patients with AD and healthy volunteers, this study shows that the serum level of soluble (s) OX40 is decreased in patients with AD, and the expression of OX40 by activated skin-homing CD4 + T cells is increased. This study further shows, using immunofluorescence on skin biopsies, that OX40 + and OX40L + cells are co-located within the dermis, indicating local activity of OX40/OX40L. Serum levels of sOX40 were associated with atopic diseases and, together, these results support that the OX40 system is important for chronic inflammation in AD skin.

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Section: Discussionsupporting

confidence: 83%

The OX40 Axis is Associated with Both Systemic and Local Involvement in Atopic Dermatitis

Elsner¹,

Carlsson²,

Stougaard³

et al. 2020

Acta Derm Venerol

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“…And OX40-mediated costimulation signals have a major part in the primary and secondary immune responses of T cells. These signals can promote the activation, proliferation, and migration of CD4+ T cells and prolong their life, as well as can accelerate the formation of germinal centers and the differentiation and maturation of cells [ 15 , 17 ]. The OX40 expression is associated with specific T cells activated by antigen.…”

Section: Introductionmentioning

confidence: 99%

OX40-Fc Fusion Protein Alleviates PD-1-Fc-Aggravated Rheumatoid Arthritis by Inhibiting Inflammatory Response

Huang

Lin

Zhan

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Researches have confirmed that the abnormal signals of OX40 and PD-1 lead to the changes of T cell biological behavior, thus participating the immunopathological process of RA. However, the pathogenesis of RA immunopathological process has not been clarified yet. Methods. 30 DBA/1 mice were randomly divided into 5 groups (6 mice per group): control group, collagen-induced arthritis (CIA) group, PD-1-Fc/CIA group, OX40-Fc/CIA group, and PD-1-Fc + OX40-Fc/CIA group. The pathological changes in mice joints were observed by H&E staining. The proportion of CD4+ T, CD8+ T, CD28+, and CD19+ cells in peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. Serum inflammatory factors (CRP, IL-2, IL-4, IL-1β, INF-γ) and bone metabolism-related genes (CTX-I, TRACP-5b, BALP) were detected by ELISA assay. Western blotting was applied to measure the NF-κB signaling pathway-related protein (p-IKKβ, p-IκBα, p50) expression in synovial tissue of mice joint. Results. Compared with the control group, CIA mice showed significant increases in arthritis score and pathological score. In the CIA group, a marked decrease was identified in the proportion of CD8+ T, CD19+, and CD68+ cells. Additionally, the CIA group was associated with upregulation of secretion of inflammatory factors in serum and expression of bone metabolism-related genes and NF-κB pathway-related proteins. Compared with the CIA group, the same indexes above showed a further aggravation in the PD-1-Fc group while all indexes improved in the OX40-Fc group. Besides, OX40-Fc fusion protein slowed down significantly the further deterioration of CIA mouse pathological process caused by PD-1-Fc fusion protein. Conclusion. OX40-Fc fusion protein alleviates PD-1-Fc-aggravated RA by inhibiting inflammatory response. This research provides biological markers with clinical significance for diagnosis and prognosis of RA, as well as offers theoretical and experimental foundation to the new targets for immune intervention.

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“…OX40/OX40L is a pair of important positive costimulatory signal molecules in the second signal system of T cells. OX40 (CD134) and OX40L (CD252), members of the TNF receptor superfamily (TNFRSF) and TNF superfamily (TNFSF), play important roles in T cell expansion in tumors, during infectious inflammation, and in autoimmune diseases [10, 11]. OX40 is expressed in activated T cells [12], while OX40L is mainly expressed in B lymphocytes, dendritic cells, and macrophage cells [12].…”

Section: Introductionmentioning

confidence: 99%

Enhancement of the Soluble Form of OX40 and OX40L Costimulatory Molecules but Reduction of the Membrane Form in Type 1 Diabetes (T1D)

Ding

et al. 2019

Journal of Immunology Research

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This study analyzed the expression of membrane OX40 and OX40L (mOX40 and mOX40L) and levels of soluble OX40 and OX40L (sOX40 and sOX40L) in T1D patients to determine their clinical significance. Peripheral blood (PB) was collected from patients with T1D and healthy control participants. Expression of mOX40 and mOX40L on immune cells was detected by flow cytometry. Levels of sOX40 and sOX40L in sera were measured by ELISA. We demonstrated for the first time enhanced sOX40 and sOX40L expression and reduced mOX40 and mOX40L levels in T1D patients which correlated with the clinical characteristics and inflammatory factors. These results suggest that OX40/OX40L signal may be promising biomarkers and associated with the pathogenesis of T1D.

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Crucial role of OX40/OX40L signaling in a murine model of asthma

Cited by 8 publications

References 61 publications

The OX40 Axis is Associated with Both Systemic and Local Involvement in Atopic Dermatitis

The OX40 Axis is Associated with Both Systemic and Local Involvement in Atopic Dermatitis

OX40-Fc Fusion Protein Alleviates PD-1-Fc-Aggravated Rheumatoid Arthritis by Inhibiting Inflammatory Response

Enhancement of the Soluble Form of OX40 and OX40L Costimulatory Molecules but Reduction of the Membrane Form in Type 1 Diabetes (T1D)

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