The Severity of CVB3-Induced Myocarditis Can Be Improved by Blocking the Orchestration of NLRP3 and Th17 in Balb/c Mice.

BACKGROUND: The functional characteristics of NLRP3 in the pathogenesis of coxsackievirus B3- (CVB3-) induced viral myocarditis (VMC) have not been fully elucidated, and the targeted therapeutic effect of NLRP3 or its related pathway in VMC has not been reported. METHOD: In this work, the change patterns of NLRP3- and Th17-related factors were detected during the pathological process of CVB3-induced VMC in Balb/c mice. The correlation between NLRP3 and Th17 cells during the VMC process was analyzed by Spearman test. The coculture system of spleen CD4+ T and bone marrow CD11c+ DC cells was set to explore the orchestration of NLRP3 and Th17 in the pathological development of VMC in vitro. Anti-IL-1ß antibody or NLRP3-/- Balb/c were used to block the NLRP3 pathway indirectly and directly to analyze the NLRP3-targeting therapeutic value. RESULTS: The change patterns of NLRP3- and Th17-related molecules in the whole pathological process of mouse CVB3-induced VMC were described. Through Spearman correlation analysis, it was confirmed that there was a close correlation between NLRP3 and Th17 cells in the whole pathological process of VMC. And the interaction mode between NLRP3 and Th17 was preliminarily explored in the cell experiment in vitro. Under the intervention of an anti-IL-1ß antibody or NLRP3 knockout, the survival rate of the intervention group was significantly improved, the degree of myocardial inflammation and fibrosis was significantly alleviated, and the content of myocardial IL-17 and spleen Th17 was also significantly decreased. CONCLUSION: Our findings demonstrated a key role of the NLRP3 inflammasome and its close relationship with Th17 in the pathological progression of CVB3-induced VMC and suggested a possible positive feedback-like mutual regulation mechanism between the NLRP3 inflammasome and Th17 in vitro and in the early stage of CVB3 infection. Taking NLRP3 as a new starting point, it provides a new target and idea for the prevention and treatment of CVB3-induced VMC.

A Critical Role for IL-21 Receptor Signaling in the Coxsackievirus B3-Induced Myocarditis.

To determine whether IL-21 receptor signaling plays a significant role in promoting Tfh cell-mediated cardiac injury in viral myocarditis (VMC), we compared IL-21R-deficient mice for some parameters of VMC. Balb/c and IL-21R-/- mice were infected with CVB3. Frequencies of splenic Tfh cells were determined by flow cytometric analysis, and productions of anti-adenine nucleotide translocator (ANT) autoantibodies were detected by enzyme-linked immunosorbent assay. To determine the effects of IL-21R signal on the proliferation of B cells, lymphocytes from spleens of the IL-21R-/- and Balb/c mice infected by CVB3 were tagged with carboxyfluorescein succinimidyl ester (CFSE) and then were stimulated with lipopolysaccharides plus IL-21 or anti-IL-21 neutralizing antibody for 3 days. The proliferation of B cells was analyzed by flow cytometry. Anti-ANT antibodies in the supernatants were detected by ELISA. Results showed that IL-21R-/- mice developed significantly less inflammation of the myocardium than Balb/c mice. Numbers of the Tfh cells and levels of anti-ANT antibody were decreased in IL-21R-/- mice, indicating IL-21 signaling plays a role on the Tfh cell response. The percentage of CD19+CFSE+ B cells decreased in IL-21R-/- mice compared to VMC mice. And anti-ANT antibodies were detected at lower levels in cultured supernatant from IL-21R-/- mice than in those from VMC mice. These data suggest that IL-21R signal may contribute to anti-ANT antibody production and expansion of B cells in VMC mice.

[A case report of giant cemento-ossifying fibroma].

Cemento-ossifying fibroma is a rare benign tumor from periodontium, which usually occurs in mandible body and mandible ramus. It consists of collagen fibrils, fibroblast, and cementoblast. This article reported a case of giant cemento-ossifying fibroma and discussed the clinical features and treatment.