IL‐3–producing basophils are required to exacerbate airway hyperresponsiveness in a murine inflammatory model

Rignault‐Bricard, Rachel; Machavoine, François; Mécheri, Salaheddine; Hermine, Olivier; Schneider, Elke; Dy, Michel; Leite‐de‐Moraes, Maria

doi:10.1111/all.13480

Cited by 20 publications

(22 citation statements)

References 42 publications

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“…lncRNAs are able to regulate inflammation by mediating recognized inflammatory mediators including TNF-a, IL-1, IL-6, and IL-18, as well as cell adhesion molecules such as ICAM-1 and VCAM-1 (29). IL-3producing basophils that could release IL-4, IL-6, and IL-13 triggered exacerbation of airway hyperresponsiveness in a murine inflammatory model (30). IFN-g causes reductions in type 2 innate lymphoid cell (ILC2) expansion and IL-13 expression thereby blocking the progression of asthma-like phenotype (31).…”

Section: Discussionmentioning

confidence: 99%

lncRNA PCGEM1 strengthens anti-inflammatory and lung protective effects of montelukast sodium in children with cough-variant asthma

Zhenxing

Meng

Xie

et al. 2020

Braz J Med Biol Res

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Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-kB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-kB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.

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Section: Discussionmentioning

confidence: 99%

lncRNA PCGEM1 strengthens anti-inflammatory and lung protective effects of montelukast sodium in children with cough-variant asthma

Zhenxing

Meng

Xie

et al. 2020

Braz J Med Biol Res

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“…Innate response activator (IRA) B cells are a subset of B1a-derived B cells that produces GM-CSF and IL-3 in infection and atherosclerosis models, thereby modulating myeloid cell differentiation and maturation [11,40,41,42]. Finally, basophils are both the target and the source of IL-3, which also act in an autocrine manner to modulate basophil survival and cytokine production [19,20].…”

Section: Biology Of Gm-csf and Il-3mentioning

confidence: 99%

“…Their role in steady-state hematopoiesis is dispensable (except for the development/maintenance of alveolar macrophages of which absence leads to pulmonary alveolar proteinosis, non-lymphoid tissue dendritic cells (DCs) and functional maturation of natural killer T cells) [4,5,6,7,8,9,10]. GM-CSF and IL-3 promote emergency myelopoiesis (i.e., generation and differentiation of myeloid cells upon infection or in the context of inflammation) [9,11,12] and also modulate effector functions of several innate immune cell subsets in vitro and in vivo [1,13,14,15,16,17,18,19,20,21]. Of note, preliminary results of clinical trials have shown that blocking antibodies against GM-CSF and IL-3-specific receptor α subunits or βc subunits can be safe and effective in several autoimmune or inflammatory diseases [1,22].…”

Section: Introductionmentioning

confidence: 99%

Innate Immune Modulation by GM-CSF and IL-3 in Health and Disease

Borriello

Galdiero

Varricchi

et al. 2019

IJMS

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Granulocyte-macrophage colony-stimulating factor (GM-CSF) and inteleukin-3 (IL-3) have long been known as mediators of emergency myelopoiesis, but recent evidence has highlighted their critical role in modulating innate immune effector functions in mice and humans. This new wealth of knowledge has uncovered novel aspects of the pathogenesis of a range of disorders, including infectious, neoplastic, autoimmune, allergic and cardiovascular diseases. Consequently, GM-CSF and IL-3 are now being investigated as therapeutic targets for some of these disorders, and some phase I/II clinical trials are already showing promising results. There is also pre-clinical and clinical evidence that GM-CSF can be an effective immunostimulatory agent when being combined with anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) in patients with metastatic melanoma as well as in novel cancer immunotherapy approaches. Finally, GM-CSF and to a lesser extent IL-3 play a critical role in experimental models of trained immunity by acting not only on bone marrow precursors but also directly on mature myeloid cells. Altogether, characterizing GM-CSF and IL-3 as central mediators of innate immune activation is poised to open new therapeutic avenues for several immune-mediated disorders and define their potential in the context of immunotherapies.

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“…Basophils, eosinophils and mast cells are classically considered as harmful components in allergies and asthma [3][4][5]. However, these cells also play important physiological roles in the coordination of defense responses against parasitic infections, tissue repair, tumor control, angiogenesis, among others [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Granulocyte-targeted therapies for airway diseases

Tavares

Peh

Tan

et al. 2020

Pharmacological Research

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The average respiration rate for an adult is 12-20 breaths per minute, which constantly exposes the lungs to allergens and harmful particles. As a result, respiratory diseases, which includes asthma, chronic obstructive pulmonary disease (COPD) and acute lower respiratory tract infections (LTRI), are a major cause of death worldwide. Although asthma, COPD and LTRI are distinctly different diseases with separate mechanisms of disease progression, they do share a common featureairway inflammation with intense recruitment and activation of granulocytes and mast cells. Neutrophils, eosinophils, basophils, and mast cells are crucial players in host defense against pathogens and maintenance of lung homeostasis. Upon contact with harmful particles, part of the pulmonary defense mechanism is to recruit these cells into the airways. Despite their protective nature, overactivation or accumulation of granulocytes and mast cells in the lungs results in unwanted chronic airway inflammation and damage. As such, understanding the bright and the dark side of these leukocytes in lung physiology paves the way for the development of therapies targeting this important mechanism of disease. Here we discuss the role of granulocytes in respiratory diseases and summarize therapeutic strategies focused on granulocyte recruitment and activation in the lungs.

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IL‐3–producing basophils are required to exacerbate airway hyperresponsiveness in a murine inflammatory model

Abstract: IL-3-dependent basophils promote Th2 allergic AHR, which designates the IL-3/basophil axis as a promising therapeutic target for the treatment of basophil-dependent asthma.

Cited by 20 publications

References 42 publications

lncRNA PCGEM1 strengthens anti-inflammatory and lung protective effects of montelukast sodium in children with cough-variant asthma

lncRNA PCGEM1 strengthens anti-inflammatory and lung protective effects of montelukast sodium in children with cough-variant asthma

Innate Immune Modulation by GM-CSF and IL-3 in Health and Disease

Granulocyte-targeted therapies for airway diseases

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