B Cell IL-4 Drives Th2 Responses In Vivo, Ameliorates Allograft Rejection, and Promotes Allergic Airway Disease

Song, Zhixing; Yuan, Wenjia; Zheng, Leting; Wang, Xingan; Kuchroo, Vijay K.; Mohib, Kanishka; Rothstein, David M.

doi:10.3389/fimmu.2022.762390

Cited by 6 publications

(8 citation statements)

References 51 publications

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“…IL-4, mainly secreted by Th2 cells [ 31 , 32 ], plays a critical role in asthma as a characteristic factor of Th2 cell subsets. IL-4 acts on B lymphocytes to produce IgE and induce a shift from IgM to IgE antibodies produced by B cells, contributing to the asthmatic response [ 33 ]. Th2 cells directly trigger the aggregation and activation of inflammatory cells by releasing IL-4, IL-5, IL-13, and other cytokines, and promote the occurrence of delayed airway allergic reactions.…”

Section: Discussionmentioning

confidence: 99%

The protective effects of Arctiin in asthma by attenuating airway inflammation and inhibiting p38/NF-κB signaling

Yuan,

Sun

2024

Aging

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Asthma is a common chronic inflammatory disease of the airways, which affects millions of people worldwide. Arctiin, a bioactive molecule derived from the traditional Chinese Burdock, has not been previously reported for its effects on asthma in infants. In this study, an asthma model was established in mice by stimulation with ovalbumin (OVA). Bronchoalveolar lavage (BALF) was collected from OVA-challenged mice and the cells were counted. Lung tissue was harvested for hematoxylin-eosin (HE) staining and measurement of Wet/Dry weight ratios. The expressions of proteins were detected using enzyme-linked immunosorbent assay (ELISA) and Western blots. The superoxide dismutase (SOD) activity in lung tissue was measured using a commercial kit. We found that Arctiin had beneficial effects on asthma treatment. Firstly, it attenuated OVA-challenged lung pathological alterations. Secondly, it ameliorated pro-inflammatory response by reducing the number of inflammatory cells and mitigating the imbalance of Th1/Th2 factors in the bronchoalveolar lavage (BALF) of OVA-challenged mice. Importantly, Arctiin ameliorated OVA-induced lung tissue impairment and improved lung function. Additionally, we observed that oxidative stress (OS) in the pulmonary tissue of OVA-challenged mice was ameliorated by Arctiin. Mechanistically, Arctiin prevented OVA-induced activation of p38 and nuclear factor-κB (NF-κB). Based on these findings, we conclude that Arctiin might serve as a promising agent for the treatment of asthma.

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Section: Discussionmentioning

confidence: 99%

The protective effects of Arctiin in asthma by attenuating airway inflammation and inhibiting p38/NF-κB signaling

Yuan,

Sun

2024

Aging

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“…Several studies have demonstrated that intravenous administration of a humanized anti-human IL-5 monoclonal antibody reduced the size of nasal polyps [25,26]. IL-4 determines the polarization of CD4 cells to effector Th2 cells and is an essential factor for immunoglobulin E (IgE) production [27][28][29]. IL-13 is found to be associated with mucous gland hyperplasia and epithelial remodeling [30,31].…”

Section: Excessive Type 2 Inflammatory Response In Ar and Crswnpmentioning

confidence: 99%

IL‐4/IL‐13 pathway in nasal type 2 inflammation: The central role and targeted therapy

Zhu,

Zhao,

Wang

2024

Eye & ENT Research

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Type 2 dominant inflammation in nasal mucosa is the key underlying pathophysiological mechanism of allergic rhinitis (AR) and most presentations of chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin‐4 (IL‐4) and IL‐13 share common receptor subunits and signaling molecules, which lead to various pathological changes in different cells, playing key roles in the pathogenesis of nasal type 2 inflammation. Numerous clinical trials have shown that biologics targeting key molecules of the IL‐4/IL‐13 pathway, especially IL‐4 receptor alpha, can treat CRSwNP and AR with high efficacy, and are generally well tolerated. Several biologics have been approved for the treatment of difficult‐to‐control CRSwNP, while others also show promising results. Here, we review the IL‐4/IL‐13 pathway, its role in nasal type 2 inflammation, and current targeted therapies related to the IL‐4/IL‐13 pathway, with a focus on AR and CRSwNP.

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“…22 In various preclinical transplantation models, IL-4 treatment or secretion has been shown to promote allograft survival, which was attributed to promotion of Th2 responses and reduction in Th1 frequency, 23 whilst also expanding the Treg compartment. 24 Additionally, promotion of Th2 subset predominance, whether intentional or as an off-target effect of an intervention, has been shown to ameliorate rejection in several mouse models. [25][26][27] An association between improved graft health and lowered rejection grades and a Th2-favoring shift in the Th1/Th2 balance has been demonstrated, emphasizing the potential importance of this subset balance.…”

Section: Cd4 + Th2 Subtypementioning

confidence: 99%

An Immune Atlas of T Cells in Transplant Rejection: Pathways and Therapeutic Opportunities

2023

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Short-term outcomes in allotransplantation are excellent due to technical and pharmacological advances; however, improvement in long-term outcomes has been limited. Recurrent episodes of acute cellular rejection, a primarily T cell–mediated response to transplanted tissue, have been implicated in the development of chronic allograft dysfunction and loss. Although it is well established that acute cellular rejection is primarily a CD4+ and CD8+ T cell mediated response, significant heterogeneity exists within these cell compartments. During immune responses, naïve CD4+ T cells are activated and subsequently differentiate into specific T helper subsets under the influence of the local cytokine milieu. These subsets have distinct phenotypic and functional characteristics, with reported differences in their contribution to rejection responses specifically. Of particular relevance are the regulatory subsets and their potential to promote tolerance of allografts. Unraveling the specific contributions of these cell subsets in the context of transplantation is complex, but may reveal new avenues of therapeutic intervention for the prevention of rejection.

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B Cell IL-4 Drives Th2 Responses In Vivo, Ameliorates Allograft Rejection, and Promotes Allergic Airway Disease

Cited by 6 publications

References 51 publications

The protective effects of Arctiin in asthma by attenuating airway inflammation and inhibiting p38/NF-κB signaling

The protective effects of Arctiin in asthma by attenuating airway inflammation and inhibiting p38/NF-κB signaling

IL‐4/IL‐13 pathway in nasal type 2 inflammation: The central role and targeted therapy

An Immune Atlas of T Cells in Transplant Rejection: Pathways and Therapeutic Opportunities

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