IL-33/ST2 immune responses to respiratory bacteria in pediatric asthma

Hentschke, Isabell; Graser, Anna; Melichar, Volker O.; Krause, Alexander; Zimmermann, Theodor; Kroß, Bettina; Haag, Patricia; Xepapadaki, Paraskevi; Papadopoulos, Nikolaos G.; Bogdan, Christian; Finotto, Susetta

doi:10.1038/srep43426

Cited by 24 publications

(28 citation statements)

References 38 publications

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“…Moreover, we reported recently that the bacterial colonization of the airways of these children influences ST2. In fact, ST2 was found to be up-regulated in asthmatic children with a mixed Gram-positive and Gramnegative bacterial colonization in their airways [25]. Finally, high 25(OH)-VitD3 serum levels were found to be associated with higher anti-inflammatory sST2 in control children without RV in the airways.…”

Section: Discussionmentioning

confidence: 88%

“…The recruitment of the subjects, inclusion and exclusion criteria, as well as the time-scale for clinical visits and data collection, have been described recently [24][25][26], and patient characteristics are reported in Table 1. This study was performed on the WP1-cohort set up at the Department of Molecular Pneumology in Erlangen in collaboration with the local Children's Hospital.…”

Section: Human Studiesmentioning

confidence: 99%

“…All methods in this study were performed in accordance with the relevant guidelines and regulations Two cohorts of preschool children (aged 4-6 years) with and without asthma were analysed. The recruitment of the subjects, inclusion and exclusion criteria, as well as the time-scale for clinical visits and data collection, have been described recently [24][25][26], and patient characteristics are reported in Table 1.…”

Section: Human Studiesmentioning

confidence: 99%

“…Thus, we reasoned that blood-circulating ILC2 progenitors might be present in the PBMCs of children with asthma. To investigate the relationship between circulating ILC2 and RV, we analysed RNA isolated from PBMCs from preschool children with and without asthma who were recruited in the European study Predicta in Erlangen (WP1-UKER), and cultured the cells for 48 h after a 1-h exposure in vitro to RV1b, as described previously [24,25,27]. After RNA extraction and RNA quality selection for gene arrays, the mRNA from seven children with asthma and five control children were analysed for gene arrays, as shown in Fig.…”

Section: Gene Arrays From In-vitro Rv-infected Pbmcs From Preschool Cmentioning

confidence: 99%

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Soluble ST2 regulation by rhinovirus and 25(OH)-vitamin D3 in the blood of asthmatic children

Haag

Sharma

Rauh

et al. 2018

Clinical and Experimental Immunology

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Paediatric asthma exacerbations are often caused by rhinovirus (RV). Moreover, 25(OH)-vitamin D3 (VitD3) deficiency during infancy was found associated with asthma. Here, we investigated the innate immune responses to RV and their possible modulation by 25(OH)-VitD3 serum levels in a preschool cohort of children with and without asthma. The innate lymphoid cell type 2 (ILC2)-associated marker, ST2, was found up-regulated in the blood cells of asthmatic children with low serum levels of 25(OH)-VitD3 in the absence of RV in their airways. Furthermore, in blood cells from control and asthmatic children with RV in their airways, soluble (s) ST2 (sST2) protein was found reduced. Asthmatic children with low 25(OH)-VitD3 in serum and with RV in vivo in their airways at the time of the analysis had the lowest sST2 protein levels in the peripheral blood compared to control children without RV and high levels of 25(OH)-VitD3. Amphiregulin (AREG), another ILC2-associated marker, was found induced in the control children with RV in their airways and low serum levels of 25(OH)-VitD3. In conclusion, the anti-inflammatory soluble form of ST2, also known as sST2, in serum correlated directly with interleukin (IL)-33 in the airways of asthmatic children. Furthermore, RV colonization in the airways and low serum levels of 25(OH)-VitD3 were found to be associated with down-regulation of sST2 in serum in paediatric asthma. These data indicate a counter-regulatory role of 25(OH)-VitD3 on RV-induced down-regulation of serum sST2 in paediatric asthma, which is relevant for the therapy of this disease.

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Section: Discussionmentioning

confidence: 88%

Section: Human Studiesmentioning

confidence: 99%

Section: Human Studiesmentioning

confidence: 99%

Section: Gene Arrays From In-vitro Rv-infected Pbmcs From Preschool Cmentioning

confidence: 99%

See 2 more Smart Citations

Soluble ST2 regulation by rhinovirus and 25(OH)-vitamin D3 in the blood of asthmatic children

Haag

Sharma

Rauh

et al. 2018

Clinical and Experimental Immunology

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“…As the IL-33/ST2 signaling axis promotes type 2 inflammation (30), recent research has started to define the role of ST2 in airway infections of various pathogens. Infection of bacteria such as Haemophilus influenzae and Moraxella catarrhalis has been associated with high levels of IL-33 in nasopharyngeal fluids (31). Studies using the respiratory syncytial virus (RSV) and influenza virus mouse models suggest that while blocking the IL-33/ST2 axis reduced RSV-induced lung inflammation and damage (32), it impaired lung epithelial integrity and function during influenza virus infection (33).…”

Section: St2 In Airway Infection and Inflammationmentioning

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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Respiratory infections regulated blood cells IFN‐β‐PD‐L1 pathway in pediatric asthma

Kölle

Haag

Vuorinen

et al. 2020

Immunity Inflam & Disease

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Background: Respiratory infections, in general, and rhinovirus infection specifically are the main reason for asthma exacerbation in children and programmed cell death protein 1 ligand (PD-L1) expression inhibits T cell responses. Objective: Could the interferon (IFN) type I expression in peripheral blood mononuclear cells (PBMCs) improve disease exacerbation in pediatric asthma? Results: Here we found increased level of PD-L1 messenger RNA (mRNA) in total blood cells isolated from preschool children with virus-induced asthma, with lower percentage of forced expiratory volume in 1 second and with high serum levels of the C-reactive-protein. Conclusions and Clinical Relevance: These data indicate that, in the presence of infection in the airways of preschool children, worse asthma is associated with induced PD-L1 mRNA expression in blood cells. Further, type I IFN, IFN-β, a cytokine that is involved in the clearance of infections, was found to be associated with a better lung function in asthmatic children. These data suggest that improving peripheral blood IFN type I expression in PBMCs in pediatric asthma could improve disease exacerbation due to suppressing PD-L1 expression in blood cells.

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IL-33/ST2 immune responses to respiratory bacteria in pediatric asthma

Cited by 24 publications

References 38 publications

Soluble ST2 regulation by rhinovirus and 25(OH)-vitamin D3 in the blood of asthmatic children

Soluble ST2 regulation by rhinovirus and 25(OH)-vitamin D3 in the blood of asthmatic children

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

Respiratory infections regulated blood cells IFN‐β‐PD‐L1 pathway in pediatric asthma

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