Short and dysfunctional telomeres protect from allergen‐induced airway inflammation

Piñeiro‐Hermida, Sergio; Martínez, Paula; Blasco, Marı́a A.

doi:10.1111/acel.13352

Cited by 12 publications

(16 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Noteworthy, treatment with the vehicle of NVP (DMSO) did not induce inflammation in lungs of inbred C57BL/6J mice ( Figure S2 ). In accordance, several drugs were previously reported to be dissolved in up to 5% DMSO for their use in preclinical mouse models [ 22 , 23 ].…”

Section: Resultsmentioning

confidence: 90%

IGF1R as a Potential Pharmacological Target in Allergic Asthma

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background: Asthma is a chronic lung disease characterized by reversible airflow obstruction, airway hyperresponsiveness (AHR), mucus overproduction and inflammation. Although Insulin-like growth factor 1 receptor (IGF1R) was found to be involved in asthma, its pharmacological inhibition has not previously been investigated in this pathology. We aimed to determine if therapeutic targeting of IGF1R ameliorates allergic airway inflammation in a murine model of asthma. Methods: C57BL/6J mice were challenged by house dust mite (HDM) extract or PBS for four weeks and therapeutically treated with the IGF1R tyrosine kinase inhibitor (TKI) NVP-ADW742 (NVP) once allergic phenotype was established. Results: Lungs of HDM-challenged mice exhibited a significant increase in phospho-IGF1R levels, incremented AHR, airway remodeling, eosinophilia and allergic inflammation, as well as altered pulmonary surfactant expression, all of being these parameters counteracted by NVP treatment. HDM-challenged lungs also displayed augmented expression of the IGF1R signaling mediator p-ERK1/2, which was greatly reduced upon treatment with NVP. Conclusions: Our results demonstrate that IGF1R could be considered a potential pharmacological target in murine HDM-induced asthma and a candidate biomarker in allergic asthma.

show abstract

Section: Resultsmentioning

confidence: 90%

IGF1R as a Potential Pharmacological Target in Allergic Asthma

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Conversely, in allergic diseases, the presence of shortened telomeres appears to induce airway inflammation; a positive correlation between leukocytes with shortened telomeres and inflammation in patients with severe asthma has been reported [ 100 ]. Piñeiro-Hermida et al [ 101 ] found that mice with increased TS rates due to genetic deficiencies ( G3 Tert −/− mice) or induced by 6-thio-2′-deoxyguanosine administration exhibited eosinophilia and low circulating IgE levels and that TS affects the differentiation of club cells, which are essential for eliminating harmful substances inhaled into the lungs. Tung et al [ 102 ] proposed that snoring accelerates TS in atopic patients, primarily in those with asthma and allergic rhinitis; however, a limitation of this study was that it did not identify which immune cell population is more sensitive to increased TS.…”

Section: Influence Of Immune Cells With Shorter Telomeres On Development Of Lung Diseasesmentioning

confidence: 99%

Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases

Ruíz

Flores‐González

Buendía-Roldán

et al. 2021

IJMS

View full text Add to dashboard Cite

Telomeres are localized at the end of chromosomes to provide genome stability; however, the telomere length tends to be shortened with each cell division inducing a progressive telomere shortening (TS). In addition to age, other factors, such as exposure to pollutants, diet, stress, and disruptions in the shelterin protein complex or genes associated with telomerase induce TS. This phenomenon favors cellular senescence and genotoxic stress, which increases the risk of the development and progression of lung diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, SARS-CoV-2 infection, and lung cancer. In an infectious environment, immune cells that exhibit TS are associated with severe lymphopenia and death, whereas in a noninfectious context, naïve T cells that exhibit TS are related to cancer progression and enhanced inflammatory processes. In this review, we discuss how TS modifies the function of the immune system cells, making them inefficient in maintaining homeostasis in the lung. Finally, we discuss the advances in drug and gene therapy for lung diseases where TS could be used as a target for future treatments.

show abstract

“…Another observation of interest is the shortening of telomere length in peripheral leukocytes of asthmatics ( 223 , 224 ), suggesting extensive leukocyte proliferation and found to correlate with eotaxin 1 expression ( 225 ). However, telomerase-deficient mice showed debilitating eosinophil responses in the lung and reduced eosinopoiesis, although eosinophil-independent effects of telomerase cannot be excluded ( 226 ). Whether constant eosinopoiesis in long-term severe asthmatics induces inflammaging phenotypes in eosinophils remains unknown.…”

Section: Phases Of Allergic Lung Inflammationmentioning

confidence: 99%

Pulmonary Eosinophils at the Center of the Allergic Space-Time Continuum

Schetters

Schuijs

2021

Front. Immunol.

View full text Add to dashboard Cite

Eosinophils are typically a minority population of circulating granulocytes being released from the bone-marrow as terminally differentiated cells. Besides their function in the defense against parasites and in promoting allergic airway inflammation, regulatory functions have now been attributed to eosinophils in various organs. Although eosinophils are involved in the inflammatory response to allergens, it remains unclear whether they are drivers of the asthma pathology or merely recruited effector cells. Recent findings highlight the homeostatic and pro-resolving capacity of eosinophils and raise the question at what point in time their function is regulated. Similarly, eosinophils from different physical locations display phenotypic and functional diversity. However, it remains unclear whether eosinophil plasticity remains as they develop and travel from the bone marrow to the tissue, in homeostasis or during inflammation. In the tissue, eosinophils of different ages and origin along the inflammatory trajectory may exhibit functional diversity as circumstances change. Herein, we outline the inflammatory time line of allergic airway inflammation from acute, late, adaptive to chronic processes. We summarize the function of the eosinophils in regards to their resident localization and time of recruitment to the lung, in all stages of the inflammatory response. In all, we argue that immunological differences in eosinophils are a function of time and space as the allergic inflammatory response is initiated and resolved.

show abstract

Short and dysfunctional telomeres protect from allergen‐induced airway inflammation

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 12 publications

References 71 publications

IGF1R as a Potential Pharmacological Target in Allergic Asthma

IGF1R as a Potential Pharmacological Target in Allergic Asthma

Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases

Pulmonary Eosinophils at the Center of the Allergic Space-Time Continuum

Contact Info

Product

Resources

About