期刊
AGING CELL
卷 20, 期 5, 页码 -出版社
WILEY
DOI: 10.1111/acel.13352
关键词
6‐ thio‐ dG; allergy; house dust mite (HDM); telomerase; telomeres
资金
- European Research Council (ERC)
- Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation [DTS17/00152]
- European Regional Development Fund (ERDF) [DTS17/00152]
- Spanish Government through the Instituto de Salud Carlos III (ISCIII)
- Spanish Estate Research Agency, Spanish Ministry of Science and Innovation [RETOS SAF2017-82623-R]
- European Regional Development Fund (ERDF)
- RyPSE-CM Programme [B2017/BMD-3770, SAF2017-82623-R]
- Fundacion Botin
- Fundacion Banco Santander (Spain)
- Comunity of Madrid
- European Social Fund
- European Regional Development Fund
- Fundacion Banco Santander
- Instituto de Salud Carlos III [DTS17/00152]
- European Regional Development Fund [B2017/BMD-3770]
- Spanish Ministry of Science and Innovation
- European Research Council [ERC-AvG882385]
The study suggests that short or dysfunctional telomeres play a protective role in murine asthma by reducing airway hyperresponsiveness and mucus secretion following exposure to allergens.
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.
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