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Wei Wang, Jonathan Cohen, Kenneth Trieu, Yan Bai, Xingbin Ai, The crosstalk between developing sympathetic nerves and immune cells contributes to early-life Th2 bias in the lung, The Journal of Immunology, Volume 200, Issue Supplement_1, May 2018, Page 44.22, https://doi.org/10.4049/jimmunol.200.Supp.44.22
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Abstract
The adaptive immunity in early life is polarized towards Th2 response, which contributes to increased susceptibility to asthma in children. However, the molecular mechanism of age-related Th2 bias remains poorly understood. Building upon critical roles of nerves in the modulation of immune responses, we investigated the crosstalk between the developing nervous system and the immune cells in postnatal lungs using murine models and human lung tissues/cells. Notably, like human, mice exhibit similar early-life Th2 bias, as allergen exposure elicits more robust inflammation in neonates than in adult mice. In addition, our previous studies revealed a similar profile of neurogenic factors between mouse and human lungs. Therefore, the neonatal mouse model of asthma provides an invaluable tool to identify potential modulatory roles of nerves in early life Th2 immunity bias. In this study, we identified dopamine as a potent inducer of Th2 phenotypes in a screen for the role of neurotransmitters in the differentiation of CD4+ T cells, which is consistent with a previous finding. Dopamine is selectively expressed by the sympathetic nerves in developing lungs. Besides, we discovered that sympathetic nerves transited from dopamine-producing in early life to norepinephrine-producing in adult life. We proved that the dopamine-rich sympathetic nerve played a role in allergic Th2 inflammation in neonatal mice lungs. However, with age, the level of dopamine decreased and therefore, this immune modulation reduced. Taken together, our findings reveal the crosstalk between the developing nerves and Th2 prone immunity in early life. Our study may provide the foundation for potential therapy strategies for kids with asthma.
