Splenic Denervation Attenuates Repeated Social Defeat Stress-Induced T Lymphocyte Inflammation

BACKGROUND: Posttraumatic stress disorder (PTSD) is a devastating psychological disorder. Patients with PTSD canonically demonstrate an increased risk for inflammatory diseases as well as increased sympathetic tone and norepinephrine outflow. Yet, the exact etiology and causal nature of these physiologic changes remain unclear. Previously, we demonstrated that exogenous norepinephrine alters mitochondrial superoxide in T lymphocytes to produce a proinflammatory T helper 17 phenotype and observed similar T helper 17 polarization in a preclinical model of PTSD. Therefore, we hypothesized sympathetic-driven neuroimmune interactions could mediate psychological trauma–induced T lymphocyte inflammation. METHODS: Repeated social defeat stress (RSDS) is a preclinical murine model that recapitulates the behavioral, autonomic, and inflammatory aspects of PTSD. Targeted splenic denervation was performed to deduce the contribution of splenic sympathetic nerves to RSDS-induced inflammation. Denervation or sham operation was performed in 85 C57BL/6J mice, followed by RSDS or control paradigms. Animals were assessed for behavioral, autonomic, inflammatory, and redox profiles. RESULTS: Denervation did not alter the antisocial or anxiety-like behavior induced by RSDS. In circulation, denervation/RSDS animals exhibited diminished levels of T lymphocyte–specific cytokines (interleukin 2 [IL-2], IL-17A, and IL-22) compared with intact animals, whereas other nonspecific inflammatory cytokines (e.g., IL-6, tumor necrosis factor α, and IL-10) were unaffected by denervation. Importantly, denervation specifically ameliorated the increases in RSDS-induced T lymphocyte mitochondrial superoxide, T helper 17 polarization, and proinflammatory gene expression with minimal impact to non–T lymphocyte immune populations. CONCLUSIONS: Overall, our data suggest that sympathetic nerves regulate RSDS-induced splenic T lymphocyte inflammation but play less of a role in the behavioral and non–T lymphocyte inflammatory phenotypes induced by this psychological trauma paradigm.