Vagus nerve plays a pivotal role in CD4+ T cell differentiation during CVB3-induced murine acute myocarditis.

Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101531386 Publication Model: Print Cited Medium: Internet ISSN: 2150-5608 (Electronic) Linking ISSN: 21505594 NLM ISO Abbreviation: Virulence Subsets: MEDLINE

Publication: 2015- : Philadelphia, PA : Taylor & Francis
Original Publication: Austin, Tex. : Landes Bioscience

CD4-Positive T-Lymphocytes/*physiology ; Cell Differentiation/*immunology ; Coxsackievirus Infections/*immunology ; Enterovirus B, Human/*immunology ; Myocarditis/*immunology ; Myocarditis/*virology ; Vagus Nerve/*immunology; Acute Disease ; Animals ; CD4-Positive T-Lymphocytes/immunology ; Cytokines/immunology ; Enterovirus B, Human/classification ; Male ; Mice ; Mice, Inbred BALB C

Abnormalities in CD4 ⁺ T cell (Th cell) differentiation play an important role in the pathogenesis of viral myocarditis (VMC). Our previous studies demonstrated that activation of the cholinergic anti-inflammatory pathway (CAP) alleviated the inflammatory response. In addition, we observed that right cervical vagotomy aggravates VMC by inhibiting CAP. However, the vagus nerve's effect on differentiation of CD4 ⁺ T cells has not been studied in VMC mice to date. In this study, we investigated the effects of cervical vagotomy and the α7nAChR agonist pnu282987 on CD4 ⁺ T cell differentiation in a murine myocarditis model (BALB/c) infected with coxsackievirus B3 (CVB3). Splenic CD4 ⁺ T cells from CVB3-induced mice obtained and cultured to investigate the potential mechanism of CD4 ⁺ T cell differentiation. Each Th cell subset was analyzed by flow cytometry. Our results showed that right cervical vagotomy increased proportions of Th1 and Th17 cells and decreased proportions of Th2 and Treg cells in the spleen. Vagotomy-induced upregulation of T-bet, Ror-γ, IFN-γ, and IL-17 expression while downregulating the expression of Gata3, Foxp3, and IL-4 in the heart. In addition, we observed upregulated levels of proinflammatory cytokines, aggravated myocardial lesions and cellular infiltration, and worsened cardiac function in VMC mice. Pnu282987 administration reversed these outcomes. Furthermore, vagotomy inhibited JAK2-STAT3 activation and enhanced NF-κB activation in splenic CD4 ⁺ T cells. The CD4 ⁺ T cell differentiation was related to JAK2-STAT3 and NF-κB signal pathways. In conclusion, vagus nerve modulates the inflammatory response by regulating CD4 ⁺ T cell differentiation in response to VMC.

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Keywords: CD4+ T cells; Viral myocarditis; cholinergic anti-inflammatory pathway; vagus nerve

0 (Cytokines)

Date Created: 20201231 Date Completed: 20210930 Latest Revision: 20210930

20221213

PMC7834089

10.1080/21505594.2020.1869384

33380272