| First Author | Piñeiro-Hermida S | Year | 2021 |
| Journal | Aging Cell | Volume | 20 |
| Issue | 5 | Pages | e13352 |
| PubMed ID | 33942458 | Mgi Jnum | J:306985 |
| Mgi Id | MGI:6712539 | Doi | 10.1111/acel.13352 |
| Citation | Pineiro-Hermida S, et al. (2021) Short and dysfunctional telomeres protect from allergen-induced airway inflammation. Aging Cell 20(5):e13352 |
| abstractText | Asthma is a chronic inflammatory disease affecting 300 million people worldwide. As telomere shortening is a well-established hallmark of aging and that asthma incidence decreases with age, here we aimed to study the role of short telomeres in asthma pathobiology. To this end, wild-type and telomerase-deficient mice with short telomeres (third-generation (G3 Tert(-/-) mice)) were challenged with intranasal house dust mite (HDM) extract. We also challenged with HDM wild-type mice in which we induced a telomere dysfunction by the administration of 6-thio-2 -deoxyguanosine (6-thio-dG). Following HDM exposure, G3 Tert(-/-) and 6-thio-dG treated mice exhibited attenuated eosinophil counts and presence of hematopoietic stem cells in the bone marrow, as well as lower levels of IgE and circulating eosinophils. Accordingly, both G3 Tert(-/-) and 6-thio-dG treated wild-type mice displayed reduced airway hyperresponsiveness (AHR), as indicated by decreased airway remodeling and allergic airway inflammation markers in the lung. Furthermore, G3 Tert(-/-) and 6-thio-dG treated mice showed lower differentiation of Club cells, attenuating goblet cell hyperplasia. Club cells of G3 Tert(-/-) and 6-thio-dG treated mice displayed increased DNA damage and senescence and reduced proliferation. Thus, short/dysfunctional telomeres play a protective role in murine asthma by impeding both AHR and mucus secretion after HDM exposure. Therefore, our findings imply that telomeres play a relevant role in allergen-induced airway inflammation. |
