Experimental asthma persists in IL-33 receptor knockout mice because of the emergence of thymic stromal lymphopoietin–driven IL-9+ and IL-13+ type 2 innate lymphoid cell subpopulations

Verma, Mukesh; Liu, Sucai; Michalec, Lidia; Sripada, Anand; Górska, M.; Alam, Rafeul

doi:10.1016/j.jaci.2017.10.020

Cited by 57 publications

(64 citation statements)

References 42 publications

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“…In mouse models, a TSLP/basophil axis has been shown to be important in experimental EoE and food allergy (44)(45)(46), and TSLP drove basophil hematopoiesis independent of IL-3 (47). In some models, TSLP-driven allergic inflammation was mediated by ILCs (48,49). Given the importance of respiratory virus infections in driving asthma exacerbations, it is interesting to note that respiratory viruses can induce TSLP expression, and type I interferons induced during the antiviral response can play a counterregulatory role by modulating ILC2 activity (50)(51)(52).…”

Section: Tslpmentioning

confidence: 99%

Epithelial cell–derived cytokines: more than just signaling the alarm

Roan

Obata-Ninomiya

Ziegler

2019

Journal of Clinical Investigation

350

272

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Section: Tslpmentioning

confidence: 99%

Epithelial cell–derived cytokines: more than just signaling the alarm

Roan

Obata-Ninomiya

Ziegler

2019

Journal of Clinical Investigation

350

272

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“…ST2 knockout (KO) mice were initially generated by the McKenzie group (47) using the replacement vector targeting ST2 gene exons 4 and 5. Although the initial genetic background of ST2 KO mice was 129ϫC57BL/6, in our previous publication the mice were then backcrossed to BALB/c mice for more than 8 generations (48). Thus, BALB/c mice were used as the wild-type control mice in the current study.…”

Section: Methodsmentioning

confidence: 99%

Interleukin 1 Receptor-Like 1 (IL1RL1) Promotes Airway Bacterial and Viral Infection and Inflammation

et al. 2019

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Interleukin 1 receptor-like 1 (IL1RL1), also known as suppression of tumorigenicity 2 (ST2), is the receptor for interleukin 33 (IL-33) and has been increasingly studied in type 2 inflammation. An increase in airway IL-33/ST2 signaling in asthma has been associated with eosinophilic inflammation, but little is known about the role of ST2 in neutrophilic inflammation. Airway Mycoplasma pneumoniae and human rhinovirus (HRV) infections are linked to neutrophilic inflammation during acute exacerbations of asthma. However, whether ST2 contributes to M. pneumoniae-and HRV-mediated airway inflammation is poorly understood. The current study sought to determine the functions of ST2 during airway M. pneumoniae or HRV infection. In cultured normal human primary airway epithelial cells, ST2 overexpression (OE) increased the production of neutrophilic chemoattractant IL-8 in the absence or presence of M. pneumoniae or HRV1B infection. ST2 OE also enhanced HRV1B-induced IP-10, a chemokine involved in asthma exacerbations. In the M. pneumoniae-infected mouse model, ST2 deficiency, in contrast to sufficiency, significantly reduced the levels of neutrophils following acute (Յ24 h) infection, while in the HRV1B-infected mouse model, ST2 deficiency significantly reduced the levels of proinflammatory cytokines KC, IP-10, and IL-33 in bronchoalveolar lavage (BAL) fluid. Overall, ST2 overexpression in human epithelial cells and ST2 sufficiency in mice increased the M. pneumoniae and HRV loads in cell supernatants and BAL fluid. After pathogen infection, ST2-deficient mice showed a higher level of the host defense protein lactotransferrin in BAL fluid. Our data suggest that ST2 promotes proinflammatory responses (e.g., neutrophils) to airway bacterial and viral infection and that blocking ST2 signaling may broadly attenuate airway infection and inflammation.

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“…Because adaptive immunity is immature in the postnatal stage, ILC2s play pivotal roles in the induction of the type 2 immune response, resulting in the development of airway hyperresponsiveness in mice . ILC2s preferentially reside in the lung and produce large amounts of Th2 cytokines, such as IL‐5 and IL‐13, in response to IL‐33, IL‐25, and thymic stromal lymphopoietin (TSLP) in a synergistic manner . ST2 + CD4 + T cells also reside in the lung with the high expression of CD44 and low expression of CD62L .…”

Section: Th2 Cells and Ilc2s Play A Distinct Role In Il‐33‐related Eomentioning

confidence: 99%

The pathogenicity of IL-33 on steroid-resistant eosinophilic inflammation via the activation of memory-type ST2+CD4+ T cells

Hirahara

Mato

Hagiwara

et al. 2018

Journal of Leukocyte Biology

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The lungs are the primary organs of the respiratory system in many animals and have unique epithelial barrier systems to protect the host from continuous invasion of various harmful particles, such as viruses and bacteria. IL-33, a member of the IL-1 family of cytokines, is released from epithelial cells in the mucosal organs and drives the type 2 immune response by activating a number of immune cells in cases of helminth infection. However, IL-33 derived from epithelial cells also causes various allergic diseases via the activation of ST2-positive immune cells, including memory-type (CD62L CD44 ) ST2 CD4 T cells in the lung. Recent studies have revealed that the type 2 inflammation induced by IL-33 is steroid resistant. Steroid resistance causes severe chronic inflammatory diseases, such as intractable asthma. In this review, we will discuss the impact of ST2 CD4 T cells on shaping the pathology of IL-33-induced eosinophilic inflammation. We will also highlight the mechanism underlying steroid resistance in eosinophilic pneumonia. A better understanding of the cellular and molecular mechanisms underlying steroid resistance is crucial for the development of new therapeutic strategies for intractable allergic diseases.

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Experimental asthma persists in IL-33 receptor knockout mice because of the emergence of thymic stromal lymphopoietin–driven IL-9+ and IL-13+ type 2 innate lymphoid cell subpopulations

Abstract: Genetic deletion of the IL-33 receptor paradoxically increases TSLP production, which stimulates the emergence of IL-9 and IL-13 ILC2s and mast cells and leads to development of chronic experimental asthma. An anti-TSLP antibody abrogates all pathologic features of asthma in this model.

Cited by 57 publications

References 42 publications

Epithelial cell–derived cytokines: more than just signaling the alarm

Epithelial cell–derived cytokines: more than just signaling the alarm

Interleukin 1 Receptor-Like 1 (IL1RL1) Promotes Airway Bacterial and Viral Infection and Inflammation

The pathogenicity of IL-33 on steroid-resistant eosinophilic inflammation via the activation of memory-type ST2+CD4+ T cells

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