Natural helper cells contribute to pulmonary eosinophilia by producing IL-13 via IL-33/ST2 pathway in a murine model of respiratory syncytial virus infection

Liu, Jing; Wu, Jianqing; Qi, Feifei; Zhang, Sheng; Liu, Xu; Hu, Haiyan; Wang, Dandan; Liu, Beixing

doi:10.1016/j.intimp.2015.05.035

Cited by 34 publications

(38 citation statements)

References 41 publications

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“…Respiratory viruses such as rhinoviruses (RV), influenza, and respiratory syncytial virus (RSV) exacerbate asthma symptoms in many patients with asthma, and it has been shown that they can induce airway inflammation through activation of ILC2s. 57 In addition, viral infections in children increase risk of subsequent development of asthma. 54 Viruses can damage airway epithelium and mediate type 2 immunity through synergistic effects resulting from regulation of the IL-25 and IL-33 pathways.…”

Section: Role Of Ilc2s In Viral-induced Type 2 Allergic Immune Respmentioning

confidence: 99%

Are ILC2s Jekyll and Hyde in airway inflammation?

Ealey

Moro

Koyasu

2017

Immunological Reviews

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Asthma is a complex heterogeneous disease of the airways characterized by lung inflammation, airway hyperreactivity (AHR), mucus overproduction, and remodeling of the airways. Group 2 innate lymphoid cells (ILC2s) play a crucial role in the initiation and propagation of type 2 inflammatory programs in allergic asthma models, independent of adaptive immunity. In response to allergen, helminths or viral infection, damaged airway epithelial cells secrete IL-33, IL-25, and thymic stromal lymphopoietin (TSLP), which activate ILC2s to produce type 2 cytokines such as IL-5, IL-13, and IL-9. Furthermore, ILC2s coordinate a network of cellular responses and interact with numerous cell types to propagate the inflammatory response and repair lung damage. ILC2s display functional plasticity in distinct asthma phenotypes, enabling them to respond to very different immune microenvironments. Thus, in the context of non-allergic asthma, triggered by exposure to environmental factors, ILC2s transdifferentiate to ILC1-like cells and activate type 1 inflammatory programs in the lung. In this review, we summarize accumulating evidence on the heterogeneity, plasticity, regulatory mechanisms, and pleiotropic roles of ILC2s in allergic inflammation as well as mechanisms for their suppression in the airways.

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Section: Role Of Ilc2s In Viral-induced Type 2 Allergic Immune Respmentioning

confidence: 99%

Are ILC2s Jekyll and Hyde in airway inflammation?

Ealey

Moro

Koyasu

2017

Immunological Reviews

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“…Additionally, increased IL-25 secretion and ILC2 activation have been reported after RV infection in neonatal mice [105]. Another study found that RSV infection in mice induced ILC2 IL-13 production in an IL-33-ST2-dependent manner [106]. Importantly, there is one human study that investigated IL-33 production and ILC2 activation after in vivo rhinovirus challenges performed in asthmatics and controls [107••].…”

Section: Ilc2 Responses Induced By Allergens and Virusesmentioning

confidence: 99%

Insights into Group 2 Innate Lymphoid Cells in Human Airway Disease

Karta

Broide

Doherty

2016

Curr Allergy Asthma Rep

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Recent discoveries have led to the identification of a novel group of immune cells, the innate lymphoid cells (ILCs). The members of this group are divided into three subpopulations: ILC1s, ILC2s, and ILC3s. ILC2s produce Th2 cytokines, IL-4, IL-5, and IL-13, upon activation by epithelial cell-derived cytokines, lipid mediators (cysteinyl leukotrienes and prostaglandin D2), and TNF family member TL1A and promote structural and immune cell responses in the airways after antigen exposure. In addition, ILC2 function is also influenced by inducible T cell costimulator (ICOS)/ ICOS-ligand (ICOS-L) interactions via direct contact between immune cells. The most common airway antigens are allergens and viruses which are highly linked to the induction of airway diseases with underlying type 2 inflammation including asthma and allergic rhinitis. Based on recent findings linking ILC2s and airway Th2 responses, there is intensive investigation into the role of ILC2s in human disease with the hope of a better understanding of the pathophysiology and the discovery of novel potential therapeutic targets. This review summarizes the recent advances made in elucidating ILC2 involvement in human Th2 airway disease.

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“…Pulmonary eosinophilia and elevated lung IL-5 levels are features of RSV infection, with some studies suggesting that they are required for airway inflammation in murine models. 23,51 Clinically, BALF IL-5 positively correlates to eosinophil level in PBMC. 12 RSVdriven eosinophil activity positively correlates to wheezing illness in patients.…”

Section: Discussionmentioning

confidence: 99%

“…21 ILC2s are activated by epithelial-derived cytokines, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) through their cognate receptors, IL17RB, ST2, and TSLPR, respectively, and produce copious amounts of the Th2 cytokines IL-13 and IL-5. 22 Previous study has demonstrated that viral infection expands ILC2 population 23 and that they are the major source of IL-5 24 and IL-13 25 contributing to the development of eosinophilia and AHR, respectively. IL-33 is a nuclear cytokine that is constitutively expressed in structural cells like type 2 pneumocytes in mice and lung epithelial cells in humans 26 and can be induced in hematopoietic cells.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary IL‐33 orchestrates innate immune cells to mediate respiratory syncytial virus‐evoked airway hyperreactivity and eosinophilia

Lai

Chi

et al. 2019

Allergy

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Background: Respiratory syncytial virus (RSV) infection is epidemiologically linked to asthma. During RSV infection, IL-33 is elevated and promotes immune cell activation, leading to the development of asthma. However, which immune cells are responsible for triggering airway hyperreactivity (AHR), inflammation and eosinophilia remained to be clarified. We aimed to elucidate the individual roles of IL-33-activated innate immune cells, including ILC2s and ST2 + myeloid cells, in RSV infection-triggered pathophysiology. Methods:The role of IL-33/ILC2 axis in RSV-induced AHR inflammation and eosinophilia were evaluated in the IL-33-deficient and YetCre-13 Rosa-DTA mice. Myeloidspecific, IL-33-deficient or ST2-deficient mice were employed to examine the role of IL-33 and ST2 signaling in myeloid cells. Results:We found that IL-33-activated ILC2s were crucial for the development of AHR and airway inflammation, during RSV infection. ILC2-derived IL-13 was sufficient for RSV-driven AHR, since reconstitution of wild-type ILC2 rescued RSV-driven AHR in IL-13-deficient mice. Meanwhile, myeloid cell-derived IL-33 was required for airway inflammation, ST2 + myeloid cells contributed to exacerbation of airway inflammation, suggesting the importance of IL-33 signaling in these cells. Local and peripheral eosinophilia is linked to both ILC2 and myeloid IL-33 signaling. Conclusions:This study highlights the importance of IL-33-activated ILC2s in mediating RSV-triggered AHR and eosinophilia. In addition, IL-33 signaling in myeloid cells is crucial for airway inflammation. K E Y W O R D S asthma, eosinophilia, IL-33, ILC2, respiratory syncytial virus | 819 WU et al.

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Natural helper cells contribute to pulmonary eosinophilia by producing IL-13 via IL-33/ST2 pathway in a murine model of respiratory syncytial virus infection

Cited by 34 publications

References 41 publications

Are ILC2s Jekyll and Hyde in airway inflammation?

Are ILC2s Jekyll and Hyde in airway inflammation?

Insights into Group 2 Innate Lymphoid Cells in Human Airway Disease

Pulmonary IL‐33 orchestrates innate immune cells to mediate respiratory syncytial virus‐evoked airway hyperreactivity and eosinophilia

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