The Role of T Cells and Macrophages in Asthma Pathogenesis: A New Perspective on Mutual Crosstalk

Zhu, Xueyi; Cui, Jie; Liu, Yi; Qin, Jingjing; Wuniqiemu, Tulake; Teng, Fangzhou; Tang, Weifeng; Wei, Ying; Dong, Jingcheng

doi:10.1155/2020/7835284

Cited by 30 publications

(21 citation statements)

References 166 publications

(173 reference statements)

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“…Asthma is characterized by airway inflammation, AHR and airway remodeling ( 45 ). Although corticosteroids are used to treat airway inflammation of asthma, they still have multiple adverse reactions, such as infections, diabetes and osteoporosis ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

Cycloastragenol alleviates airway inflammation in asthmatic mice by inhibiting autophagy

Zhu

Cao

Su³

et al. 2021

Mol Med Rep

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Cycloastragenol (CAG), a secondary metabolite from the roots of Astragalus zahlbruckneri , has been reported to exert anti-inflammatory effects in heart, skin and liver diseases. However, its role in asthma remains unclear. The present study aimed to investigate the effect of CAG on airway inflammation in an ovalbumin (OVA)-induced mouse asthma model. The current study evaluated the lung function and levels of inflammation and autophagy via measurement of airway hyperresponsiveness (AHR), lung histology examination, inflammatory cytokine measurement and western blotting, amongst other techniques. The results demonstrated that CAG attenuated OVA-induced AHR in vivo . In addition, the total number of leukocytes and eosinophils, as well as the secretion of inflammatory cytokines, including interleukin (IL)-5, IL-13 and immunoglobulin E were diminished in bronchoalveolar lavage fluid of the OVA-induced murine asthma model. Histological analysis revealed that CAG suppressed inflammatory cell infiltration and goblet cell secretion. Notably, based on molecular docking simulation, CAG was demonstrated to bind to the active site of autophagy-related gene 4-microtubule-associated proteins light chain 3 complex, which explains the reduced autophagic flux in asthma caused by CAG. The expression levels of proteins associated with autophagy pathways were inhibited following treatment with CAG. Taken together, the results of the present study suggest that CAG exerts an anti-inflammatory effect in asthma, and its role may be associated with the inhibition of autophagy in lung cells.

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Section: Discussionmentioning

confidence: 99%

Cycloastragenol alleviates airway inflammation in asthmatic mice by inhibiting autophagy

Zhu

Cao

Su³

et al. 2021

Mol Med Rep

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“…Moreover, M2a macrophages express a number of mediators associated with tissue fibrosis, particularly TGF-b (6). Moreover, macrophage-derived cytokines (IL-1b, IL-6, TSLP, IL-33) and chemokines (CCL2, CCL17, CCL22) have been shown to promote Th2 cell differentiation and recruitment (161)(162)(163)(164), indicative of a complex form of crosstalk between these immune cell types.…”

Section: Lung Macrophage Diversity and Immune Regulation In Allergic Asthmamentioning

confidence: 99%

Macrophages: The Good, the Bad, and the Gluttony

2021

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Macrophages are dynamic cells that play critical roles in the induction and resolution of sterile inflammation. In this review, we will compile and interpret recent findings on the plasticity of macrophages and how these cells contribute to the development of non-infectious inflammatory diseases, with a particular focus on allergic and autoimmune disorders. The critical roles of macrophages in the resolution of inflammation will then be examined, emphasizing the ability of macrophages to clear apoptotic immune cells. Rheumatoid arthritis (RA) is a chronic autoimmune-driven spectrum of diseases where persistent inflammation results in synovial hyperplasia and excessive immune cell accumulation, leading to remodeling and reduced function in affected joints. Macrophages are central to the pathophysiology of RA, driving episodic cycles of chronic inflammation and tissue destruction. RA patients have increased numbers of active M1 polarized pro-inflammatory macrophages and few or inactive M2 type cells. This imbalance in macrophage homeostasis is a main contributor to pro-inflammatory mediators in RA, resulting in continual activation of immune and stromal populations and accelerated tissue remodeling. Modulation of macrophage phenotype and function remains a key therapeutic goal for the treatment of this disease. Intriguingly, therapeutic intervention with glucocorticoids or other DMARDs promotes the re-polarization of M1 macrophages to an anti-inflammatory M2 phenotype; this reprogramming is dependent on metabolic changes to promote phenotypic switching. Allergic asthma is associated with Th2-polarised airway inflammation, structural remodeling of the large airways, and airway hyperresponsiveness. Macrophage polarization has a profound impact on asthma pathogenesis, as the response to allergen exposure is regulated by an intricate interplay between local immune factors including cytokines, chemokines and danger signals from neighboring cells. In the Th2-polarized environment characteristic of allergic asthma, high levels of IL-4 produced by locally infiltrating innate lymphoid cells and helper T cells promote the acquisition of an alternatively activated M2a phenotype in macrophages, with myriad effects on the local immune response and airway structure. Targeting regulators of macrophage plasticity is currently being pursued in the treatment of allergic asthma and other allergic diseases. Macrophages promote the re-balancing of pro-inflammatory responses towards pro-resolution responses and are thus central to the success of an inflammatory response. It has long been established that apoptosis supports monocyte and macrophage recruitment to sites of inflammation, facilitating subsequent corpse clearance. This drives resolution responses and mediates a phenotypic switch in the polarity of macrophages. However, the role of apoptotic cell-derived extracellular vesicles (ACdEV) in the recruitment and control of macrophage phenotype has received remarkably little attention. ACdEV are powerful mediators of intercellular communication, carrying a wealth of lipid and protein mediators that may modulate macrophage phenotype, including a cargo of active immune-modulating enzymes. The impact of such interactions may result in repair or disease in different contexts. In this review, we will discuss the origin, characterization, and activity of macrophages in sterile inflammatory diseases and the underlying mechanisms of macrophage polarization via ACdEV and apoptotic cell clearance, in order to provide new insights into therapeutic strategies that could exploit the capabilities of these agile and responsive cells.

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“…Th2 cells and ILC2s will further secrete the Th2 panel of biomarkers (IL-4, IL-5 and IL-13) responsible for eosinophilic inflammation. In this form of asthma, activation of Th1 functions acts as a regulator of Th2 activation [163].…”

Section: Inflammation and Immune Responsementioning

confidence: 99%

Adiponectin and Asthma: Knowns, Unknowns and Controversies

Oțelea

Arghir

Zugravu

et al. 2021

IJMS

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Adiponectin is an adipokine associated with the healthy obese phenotype. Adiponectin increases insulin sensitivity and has cardio and vascular protection actions. Studies related to adiponectin, a modulator of the innate and acquired immunity response, have suggested a role of this molecule in asthma. Studies based on various asthma animal models and on the key cells involved in the allergic response have provided important insights about this relation. Some of them indicated protection and others reversed the balance towards negative effects. Many of them described the cellular pathways activated by adiponectin, which are potentially beneficial for asthma prevention or for reduction in the risk of exacerbations. However, conclusive proofs about their efficiency still need to be provided. In this article, we will, briefly, present the general actions of adiponectin and the epidemiological studies supporting the relation with asthma. The main focus of the current review is on the mechanisms of adiponectin and the impact on the pathobiology of asthma. From this perspective, we will provide arguments for and against the positive influence of this molecule in asthma, also indicating the controversies and sketching out the potential directions of research to complete the picture.

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The Role of T Cells and Macrophages in Asthma Pathogenesis: A New Perspective on Mutual Crosstalk

Cited by 30 publications

References 166 publications

Cycloastragenol alleviates airway inflammation in asthmatic mice by inhibiting autophagy

Cycloastragenol alleviates airway inflammation in asthmatic mice by inhibiting autophagy

Macrophages: The Good, the Bad, and the Gluttony

Adiponectin and Asthma: Knowns, Unknowns and Controversies

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