Age-Related Dopaminergic Innervation Augments T Helper 2-Type Allergic Inflammation in the Postnatal Lung
| Autor: | Alan Fine, Fengzhi Shao, Kenneth G. Trieu, Wei Wang, Xingbin Ai, Jonathan A. Cohen, Juliana Barrios, Yan Bai, Antonia Wallrapp, Vijay K. Kuchroo, Matthew R. Jones, Nandini Krishnamoorthy |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adrenergic Neurons Male Sympathetic Nervous System medicine.medical_treatment Cellular differentiation Dopamine Mice 0302 clinical medicine STAT5 Transcription Factor Immunology and Allergy Child Lung Cells Cultured Mice Knockout Dopaminergic Age Factors Middle Aged Infectious Diseases Cytokine medicine.anatomical_structure Dopamine receptor 030220 oncology & carcinogenesis Child Preschool Female medicine.drug Adult Adolescent Neurogenesis Immunology Biology Allergic inflammation 03 medical and health sciences Th2 Cells medicine Animals Humans Interleukin 4 Aged Dopaminergic Neurons Receptors Dopamine D4 Infant Newborn Infant Asthma Mice Inbred C57BL 030104 developmental biology Interleukin-2 Interleukin-4 |
| Zdroj: | Immunity. 51(6) |
| ISSN: | 1097-4180 |
| Popis: | Summary Young children are more susceptible to developing allergic asthma than adults. As neural innervation of the peripheral tissue continues to develop after birth, neurons may modulate tissue inflammation in an age-related manner. Here we showed that sympathetic nerves underwent a dopaminergic-to-adrenergic transition during post-natal development of the lung in mice and humans. Dopamine signaled through a specific dopamine receptor (DRD4) to promote T helper 2 (Th2) cell differentiation. The dopamine-DRD4 pathway acted synergistically with the cytokine IL-4 by upregulating IL-2-STAT5 signaling and reducing inhibitory histone trimethylation at Th2 gene loci. In murine models of allergen exposure, the dopamine-DRD4 pathway augmented Th2 inflammation in the lungs of young mice. However, this pathway operated marginally after sympathetic nerves became adrenergic in the adult lung. Taken together, the communication between dopaminergic nerves and CD4+ T cells provides an age-related mechanism underlying the susceptibility to allergic inflammation in the early lung. |
| Databáze: | OpenAIRE |
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