Mitochondrial Superoxide Signaling Contributes to Norepinephrine-Mediated T-Lymphocyte Cytokine Profiles

AbstractBackgroundPost-traumatic stress disorder (PTSD) is a devastating psychological disorder that significantly increases the risk for inflammatory diseases. While the exact etiology of this predisposition remains unclear, PTSD canonically increases overall sympathetic tone resulting in increased norepinephrine (NE) outflow. Previously, we demonstrated that exogenous NE alters mitochondrial superoxide in T-lymphocytes to produce a pro-inflammatory T-helper 17 (TH17) phenotype. Therefore, we hypothesized sympathetic-driven neuroimmune interactions could mediate psychological trauma-induced T-lymphocyte inflammation.MethodsRepeated social defeat stress (RSDS) is a preclinical murine model that recapitulates the behavioral, autonomic, and inflammatory aspects of PTSD. Targeted splenic denervation (Dnx) was performed to deduce the contribution of splenic sympathetic nerves to RSDS-induced inflammation. Eighty-five C57BL/6J mice underwent Dnx or sham-operation, followed by RSDS or control paradigms. Animals were assessed for behavioral, autonomic, inflammatory, and redox profiles.ResultsDnx did not alter the antisocial or anxiety-like behavior induced by RSDS. In circulation, RSDS Dnx animals exhibited diminished levels of T-lymphocyte-specific cytokines (IL-2, IL-17A, and IL-22) compared to intact animals, whereas other non-specific inflammatory cytokines (e.g., IL-6, TNF-α, and IL-10) were unaffected by Dnx. Importantly, Dnx specifically ameliorated the increases in RSDS-induced T-lymphocyte mitochondrial superoxide, TH17 polarization, and pro-inflammatory gene expression with minimal impact to non-T-lymphocyte immune populations.ConclusionsOverall, our data suggest that sympathetic nerves regulate RSDS-induced splenic T-lymphocyte inflammation, but play a minimal role in the behavioral and non-T-lymphocyte inflammatory phenotypes induced by this psychological trauma paradigm.

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A 3-Week Dynamic Differences of Immunological Parameters in Severe and Non-severe COVID-19

10.21203/rs.3.rs-36753/v1 ◽

2020 ◽

Author(s):

Qiang Li ◽

Wei Xu ◽

Weixia Li ◽

Chenglu Huang ◽

Liang Chen

Keyword(s):

T Lymphocyte ◽

Lymphocyte Subsets ◽

Immunological Parameters ◽

T Lymphocyte Subsets ◽

Cytokine Profiles ◽

Tnf Α ◽

Severe Group ◽

Ifn Γ ◽

Low Levels

Abstract Objective We aimed to compare the dynamic differences of immunological parameters in severe and non-severe COVID-19. Methods In this study, the cytokine profiles and lymphocyte subsets of 70 patients (31 severe COVID-19 and 39 non-severe COVID-19) were longitudinally analyzed. Results Compared with non-severe cases, severe cases had higher age (64 vs 36 years, p<0.001), more common comorbidities (74.2% vs 15.4%, p<0.001), and more frequently lymphopenia (0.7 vs 1.6×109/L, p<0.001). Severe cases had markedly higher levels of IL-6, IL-8, and IL-10 than non-severe cases from baseline to 3 weeks after admission (p<0.001). No significant differences were observed in the levels of IL-1β, IL-2, IL-4, IL-5, IL-12P70, IL-17, TNF-α, IFN-α, and IFN-γ between the two groups during the follow-up (p > 0.05). The absolute numbers of CD3+, CD4+, CD8+, and CD45+ T cells were markedly lower in severe cases compared with that in non-severe cases from baseline to 3 weeks after admission (p<0.001). The decrease of T lymphocyte subsets reached its peak from day 1 to 3 after admission, and gradually increased from day 4 to 21 in the non-severe group; however, reached its peak from day 4 to 7 after admission, and sustained at a low levels in the severe group. Conclusion The dynamic changes of cytokine profiles and T lymphocyte subsets are related with the disease severity of patients with COVID-19.

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