Sympathetic nervous tone limits the development of myeloid-derived suppressor cells

Science Immunology
James T NevinPramod K Srivastava

Abstract

Sympathetic nerves that innervate lymphoid organs regulate immune development and function by releasing norepinephrine that is sensed by immune cells via their expression of adrenergic receptors. Here, we demonstrate that ablation of sympathetic nervous system (SNS) signaling suppresses tumor immunity, and we dissect the mechanism of such immune suppression. We report that disruption of the SNS in mice removes a critical α-adrenergic signal required for maturation of myeloid cells in normal and tumor-bearing mice. In tumor-bearing mice, disruption of the α-adrenergic signal leads to the accumulation of immature myeloid-derived suppressor cells (MDSCs) that suppress tumor immunity and promote tumor growth. Furthermore, we show that these SNS-responsive MDSCs drive expansion of regulatory T cells via secretion of the alarmin heterodimer S100A8/A9, thereby compounding their immunosuppressive activity. Our results describe a regulatory framework in which sympathetic tone controls the development of innate and adaptive immune cells and influences their activity in health and disease.

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Citations

Jan 5, 2021·Frontiers in Cell and Developmental Biology·Wenjun WangJiuwei Cui

Related Concepts

Cell Growth
Laboratory mice
Norepinephrine
Adrenergic Receptor
Sympathetic Nervous System
Regulatory T-Lymphocytes
Immune Effector Cell
Lymphoid Organ Structure
Ablation
Adaptive Immunity

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