Inhibition of thymocyte autophagy-associated CD4+ T thymopoiesis is involved in asthma susceptibility in mice exposed to caffeine prenatally

Archives of Toxicology
Han-Xiao LiuJie Ping

Abstract

Our previous studies demonstrated that prenatal caffeine exposure (PCE) caused thymopoiesis inhibition, immune disorders, and airway remodeling in offspring, which raises the question of whether PCE is a risk factor for postnatal asthma. Meanwhile, the mechanism of PCE-induced thymopoiesis inhibition is not clear yet. Considering caffeine's pro-autophagy effects (lacking evidence in thymus) and the important role of autophagy in maintaining thymopoiesis, this study aimed to investigate whether PCE contributes to asthma susceptibility, and further explore the molecular mechanisms of thymopoiesis inhibition from the perspective of pro-autophagy effects of caffeine both in vivo and in vitro. The PCE mouse model was established by 96 mg/kg/day caffeine administration from gestational day (GD) 9-GD 18, and an asthma model was established on the offspring by ovalbumin sensitization and challenge. The results confirmed our hypothesis that PCE could suppress pulmonary CD4+T development and aggravate allergen-induced asthma symptoms in the offspring. In fetuses, PCE significantly suppressed A2AR-PKA signaling, upregulated Beclin1-LC3II autophagy, promoted Bcl10 degradation, reduced A20 expression, and inhibited CD4+T thymopoiesis. Simil...Continue Reading

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Citations

Dec 19, 2019·Frontiers in Immunology·Karan SachdevaPeisong Gao
Jan 5, 2021·Frontiers in Neuroscience·Xiangpeng Ren, Jiang-Fan Chen

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Methods Mentioned

BETA
immunoprecipitation
bronchoalveolar lavage
enzyme-linked immunosorbent assay
Co-IP
flow cytometry
bronchoalveolar

Software Mentioned

Primer Premier
GraphPad
Prism
SPSS

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