IL-17A both initiates (via IFNγ suppression) and limits the pulmonary type-2 immune response to nematode infection

Ajendra, Jesuthas; Chenery, Alistair; Parkinson, JE; Chan, Brian H. K.; Pearson, Stella; Colombo, Stefano A. P.; Boon, Louis; Grencis, Richard K.; Sutherland, Tara E.; Allen, Judith E.

doi:10.1101/827899

Cited by 11 publications

(20 citation statements)

References 55 publications

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“…However, type 2 inflammation was reduced from week 4 to week 8, perhaps reflecting the emergence of a tolerogenic response to allergens in BALB/c mice. 25 50 In addition, IL-10 derived from T cells has been shown to signal via alveolar macrophages, leading to suppression of IFNc-induced airway epithelial disruption. 51 No difference in expression of Il10 between strains at chronic time points was observed after DRA administration in our study.…”

Section: Discussionmentioning

confidence: 99%

The magnitude of airway remodeling is not altered by distinct allergic inflammatory responses in BALB/c versus C57BL/6 mice but matrix composition differs

Parkinson

Pearson

Rückerl

et al. 2021

Immunol. Cell Biol.

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Allergic airway inflammation is heterogeneous with variability in immune phenotypes observed across asthmatic patients. Inflammation has been thought to directly contribute to airway remodeling in asthma, but clinical data suggest that neutralizing type 2 cytokines does not necessarily alter disease pathogenesis. Here, we utilized C57BL/6 and BALB/c mice to investigate the development of allergic airway inflammation and remodeling. Exposure to an allergen cocktail for up to 8 weeks led to type 2 and type 17 inflammation, characterized by airway eosinophilia and neutrophilia and increased expression of chitinase-like proteins in both C57BL/6 and BALB/c mice. However, BALB/c mice developed much greater inflammatory responses than C57BL/6 mice, effects possibly explained by a failure to induce pathways that regulate and maintain T-cell activation in C57BL/6 mice, as shown by whole lung RNA transcript analysis. Allergen administration resulted in a similar degree of airway remodeling between mouse strains but with differences in collagen subtype composition. Increased collagen III was observed around the airways of C57BL/6 but not BALB/c mice while allergen-induced loss of basement membrane collagen IV was only observed in BALB/c mice. This study highlights a model of type 2/type 17 airway inflammation in mice whereby development of airway remodeling can occur in both BALB/c and C57BL/6 mice despite differences in immune response dynamics between strains. Importantly, compositional changes in the extracellular matrix between genetic strains of mice may help us better understand the relationships between lung function, remodeling and airway inflammation.

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Section: Discussionmentioning

confidence: 99%

The magnitude of airway remodeling is not altered by distinct allergic inflammatory responses in BALB/c versus C57BL/6 mice but matrix composition differs

Parkinson

Pearson

Rückerl

et al. 2021

Immunol. Cell Biol.

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show abstract

“…Interestingly, increased IL-17A expression in C57BL/6 mice between weeks 4 and 8 coincided with a reduction in IFNγ levels in allergic mice, which we have shown previously to be an important factor that allows the development of a pulmonary type 2 immune response. 50 Additionally, IL-10 derived from T cells has been shown to signal via alveolar macrophages leading to suppression of IFNγ-induced airway epithelial disruption. 51 No difference in expression of Il10 between strains at chronic time points was observed after DRA administration in our study.…”

Section: Discussionmentioning

confidence: 99%

The magnitude of airway remodelling is not altered by distinct allergic inflammatory responses in BALB/c vs C57BL/6 mice but matrix composition differs

Parkinson

Pearson

Rückerl

et al. 2020

Preprint

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Airway inflammation in response to allergens is heterogenous with variability in immune phenotypes observed across asthmatic patients. Whilst inflammation, specifically type 2 immune responses, are thought to directly contribute to airway remodelling and pathology in asthma, clinical data suggests that neutralising type 2 cytokines do not necessarily alter disease pathogenesis. Here we show, using a mouse model allergic airway inflammation, that both C57BL/6 and BALB/c mice develop mixed type 2 and type 17 inflammation. However, BALB/c mice develop much greater inflammatory responses than C57BL/6 mice, effects possibly explained by a reduction in pathways that regulate and maintain T cell activation in C57BL/6 mice, as shown by RNA transcript analysis. Chronic allergen exposure resulted in a similar degree of airway remodelling changes such as ECM deposition and increases in goblet cells and airway muscle mass between mouse strains. However, collagen subtype composition revealed increased collagen III around of the airways of C57BL/6 but not BALB/c mice. Furthermore, allergen-induced loss of basement membrane collagen IV was only observed in BALB/c mice. This study highlights a model of type 2/type 17 airway inflammation in mice whereby development of airway remodelling can occur in both BALB/c and C57BL/6 mice despite differences in immune response dynamics between strains. Importantly, compositional differences in the ECM between genetic strains of mice may help us better understand the relationships between lung function, remodelling and airway inflammation.

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“…Other approaches have been to target specific cytokines. For example, a recent study has elucidated the role of IL-17A in the promotion of Th2 immune responses in the lung following infection with T. muris utilizing global IL-17a knockout mice (Ajendra et al ., 2020). In addition, the utilization of bone marrow chimeras and the Cre loxP system has further refined these investigations.…”

Section: Understanding Immune Responses To T Muris In Laboratory Mice: Implications For Basic and Applied Sciencementioning

confidence: 99%

Trichuris muris as a tool for holistic discovery research: from translational research to environmental bio-tagging

2021

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IL-17A both initiates (via IFNγ suppression) and limits the pulmonary type-2 immune response to nematode infection

Cited by 11 publications

References 55 publications

The magnitude of airway remodeling is not altered by distinct allergic inflammatory responses in BALB/c versus C57BL/6 mice but matrix composition differs

The magnitude of airway remodeling is not altered by distinct allergic inflammatory responses in BALB/c versus C57BL/6 mice but matrix composition differs

The magnitude of airway remodelling is not altered by distinct allergic inflammatory responses in BALB/c vs C57BL/6 mice but matrix composition differs

Trichuris muris as a tool for holistic discovery research: from translational research to environmental bio-tagging

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