Maternal diesel particle exposure promotes offspring asthma through NK cell–derived granzyme B
| Autor: | Jerica Lenberg, Magdalena M. Gorska, Bidisha Paul Chowdhury, Rafeul Alam, Qian Qian, Zehua Sun, Eric Vivier |
|---|---|
| Přispěvatelé: | National Jewish Health, University of Colorado Anschutz [Aurora], Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Innate Pharma, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Endotype Offspring [SDV]Life Sciences [q-bio] Cell Biology complex mixtures Granzymes Type 2 immune response 03 medical and health sciences Mice 0302 clinical medicine Th2 Cells Pregnancy medicine Animals Humans Receptor ComputingMilieux_MISCELLANEOUS Vehicle Emissions Mice Knockout Interleukin-13 Interleukin-17 GATA3 General Medicine respiratory system Asthma 3. Good health respiratory tract diseases Granzyme B Killer Cells Natural Disease Models Animal 030104 developmental biology medicine.anatomical_structure Maternal Exposure 030220 oncology & carcinogenesis Cord blood Prenatal Exposure Delayed Effects Immunology Female Research Article |
| Zdroj: | Journal of Clinical Investigation J Clin Invest Journal of Clinical Investigation, American Society for Clinical Investigation, 2020, ⟨10.1172/JCI130324⟩ Journal of Clinical Investigation, 2020, ⟨10.1172/JCI130324⟩ |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci130324 |
| Popis: | Mothers living near high-traffic roads before or during pregnancy are more likely to have children with asthma. Mechanisms are unknown. Using a mouse model, here we showed that maternal exposure to diesel exhaust particles (DEP) predisposed offspring to allergic airway disease (AAD, murine counterpart of human asthma) through programming of their NK cells; predisposition to AAD did not develop in DEP pups that lacked NK cells and was induced in normal pups receiving NK cells from WT DEP pups. DEP NK cells expressed GATA3 and cosecreted IL-13 and the killer protease granzyme B in response to allergen challenge. Extracellular granzyme B did not kill, but instead stimulated protease-activated receptor 2 (PAR2) to cooperate with IL-13 in the induction of IL-25 in airway epithelial cells. Through loss-of-function and reconstitution experiments in pups, we showed that NK cells and granzyme B were required for IL-25 induction and activation of the type 2 immune response and that IL-25 mediated NK cell effects on type 2 response and AAD. Finally, experiments using human cord blood and airway epithelial cells suggested that DEP might induce an identical pathway in humans. Collectively, we describe an NK cell-dependent endotype of AAD that emerged in early life as a result of maternal exposure to DEP. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|