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Age-Related Dopaminergic Innervation Augments Th2 Inflammation in the Postnatal Lung

68 Pages Posted: 19 May 2019 Sneak Peek Status: Under Review

See all articles by Wei Wang

Wei Wang

Brigham and Women's Hospital, Department of Medicine, Division of Pulmonary and Critical Care Medicine

Jonathan A. Cohen

Brigham and Women's Hospital, Department of Medicine, Division of Pulmonary and Critical Care Medicine

Kenneth G. Trieu

Brigham and Women's Hospital, Department of Medicine, Division of Pulmonary and Critical Care Medicine

Juliana Barrios

Boston University, School of Medicine, Department of Medicine, Pulmonary Center

Nandini Krishnamoorthy

Brigham and Women's Hospital, Department of Medicine, Division of Pulmonary and Critical Care Medicine

Matthew R. Jones

Boston University, School of Medicine, Department of Medicine, Pulmonary Cente

Alan Fine

Boston University, School of Medicine, Department of Medicine, Pulmonary Center; West Roxbury Veteran's Hospital

Yan Bai

Brigham and Women's Hospital, Department of Medicine, Division of Pulmonary and Critical Care Medicine

Xingbin Ai

Brigham and Women's Hospital, Department of Medicine, Division of Pulmonary and Critical Care Medicine

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Abstract

As neural innervation of the peripheral tissue continues to develop after birth, neurons may modulate tissue inflammation in an age-related manner. Herein, we investigated the role of the developing nervous system in the asthma diathesis that characterizes the early age. We showed that sympathetic nerves in the lung underwent a dopaminergic-to-adrenergic transition during postnatal development. In addition, dopamine was found to promote a T helper 2 (Th2) phenotype by signaling through a specific DRD4 receptor on CD4+ T cells. Mechanistically, the dopamine-DRD4 pathway acted synergistically with interleukin 4 (IL-4) by upregulating IL-2/STAT5 signaling and reducing inhibitory histone trimethylation at Th2 gene loci. Furthermore, in murine models of allergen exposure, we demonstrated that the dopamine-DRD4 pathway significantly augmented Th2 inflammation in the early lung, but much less so in the adult lung. Taken together, an age-related communication between dopaminergic nerves and CD4+ T cells augments Th2 inflammation in the early lung.

Keywords: allergic asthma, Th2, sympathetic nerve, dopamine, DRD4, IL-2, IL-4

Suggested Citation

Wang, Wei and Cohen, Jonathan A. and Trieu, Kenneth G. and Barrios, Juliana and Krishnamoorthy, Nandini and Jones, Matthew R. and Fine, Alan and Bai, Yan and Ai, Xingbin, Age-Related Dopaminergic Innervation Augments Th2 Inflammation in the Postnatal Lung (May 17, 2019). IMMUNITY-D-19-00506. Available at SSRN: https://ssrn.com/abstract=3389887 or http://dx.doi.org/10.2139/ssrn.3389887
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Wei Wang

Brigham and Women's Hospital, Department of Medicine, Division of Pulmonary and Critical Care Medicine

Boston, MA
United States

Jonathan A. Cohen

Brigham and Women's Hospital, Department of Medicine, Division of Pulmonary and Critical Care Medicine

Boston, MA
United States

Kenneth G. Trieu

Brigham and Women's Hospital, Department of Medicine, Division of Pulmonary and Critical Care Medicine ( email )

Boston, MA
United States

Juliana Barrios

Boston University, School of Medicine, Department of Medicine, Pulmonary Center ( email )

Boston, MA
United States

Nandini Krishnamoorthy

Brigham and Women's Hospital, Department of Medicine, Division of Pulmonary and Critical Care Medicine ( email )

Boston, MA
United States

Matthew R. Jones

Boston University, School of Medicine, Department of Medicine, Pulmonary Cente ( email )

Boston, MA
United States

Alan Fine

Boston University, School of Medicine, Department of Medicine, Pulmonary Center

Boston, MA
United States

West Roxbury Veteran's Hospital ( email )

West Roxbury, MA
United States

Yan Bai

Brigham and Women's Hospital, Department of Medicine, Division of Pulmonary and Critical Care Medicine

Boston, MA
United States

Xingbin Ai (Contact Author)

Brigham and Women's Hospital, Department of Medicine, Division of Pulmonary and Critical Care Medicine ( email )

Boston, MA
United States

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