PURPOSE: Excessive inflammation responses mediated by CD4(+) T cells contributes to myocardial fibrosis in dilated cardiomyopathy (DCM) resulting from viral myocarditis. Recently, some scholars discovered that B cells harbored an abnormal pro-inflammatory capacity besides the production of autoantibodies. Thus, we aimed to explore whether and which type of B cells act on myocardial fibrosis in DCM. METHODS: A total of 56 newly hospitalized DCM patients were studied, and among these, 17 patients accepted the gadolinium enhanced cardiovascular magnetic resonance imaging (MRI) for myocardial fibrosis evaluations. RESULTS: B cell functions including the frequency and proliferation were significantly elevated in DCM patients. After screening the important cytokines including IL-1β, IL-6, IL-10, IL-17, TNF-α and TGF-β produced in these B cells by flow cytometry, we found that only the TNF-α-secreting B cells were obviously increased. Furthermore, the TNF-α protein secretion and mRNA levels were also enhanced in LPS-stimulated B cell isolated from DCM patients. In addition, 10 patients (59%) with increased TNF-α-secreting B cells showed late enhancement and boosted serum procollagen type III compared with the other 7 patients (41%) whose enhancement could not be detected. Moreover, the frequencies of TNF-α-secreting B cells were negatively correlated with LVEF and positively correlated with LVEDD, NT-proBNP and procollagen type III in all of the DCM patients. CONCLUSIONS: Our study firstly suggested that TNF-α-secreting B cells were involved in myocardial fibrosis, which revealed the new pathogenic mechanism of B cells in DCM, and therapeutic targets against these cells might be valuable.
PURPOSE:Excessive inflammation responses mediated by CD4(+) T cells contributes to myocardial fibrosis in dilated cardiomyopathy (DCM) resulting from viral myocarditis. Recently, some scholars discovered that B cells harbored an abnormal pro-inflammatory capacity besides the production of autoantibodies. Thus, we aimed to explore whether and which type of B cells act on myocardial fibrosis in DCM. METHODS: A total of 56 newly hospitalized DCMpatients were studied, and among these, 17 patients accepted the gadolinium enhanced cardiovascular magnetic resonance imaging (MRI) for myocardial fibrosis evaluations. RESULTS: B cell functions including the frequency and proliferation were significantly elevated in DCMpatients. After screening the important cytokines including IL-1β, IL-6, IL-10, IL-17, TNF-α and TGF-β produced in these B cells by flow cytometry, we found that only the TNF-α-secreting B cells were obviously increased. Furthermore, the TNF-α protein secretion and mRNA levels were also enhanced in LPS-stimulated B cell isolated from DCMpatients. In addition, 10 patients (59%) with increased TNF-α-secreting B cells showed late enhancement and boosted serum procollagen type III compared with the other 7 patients (41%) whose enhancement could not be detected. Moreover, the frequencies of TNF-α-secreting B cells were negatively correlated with LVEF and positively correlated with LVEDD, NT-proBNP and procollagen type III in all of the DCMpatients. CONCLUSIONS: Our study firstly suggested that TNF-α-secreting B cells were involved in myocardial fibrosis, which revealed the new pathogenic mechanism of B cells in DCM, and therapeutic targets against these cells might be valuable.
Authors: Przemyslaw Blyszczuk; Gabriela Kania; Thomas Dieterle; Rene R Marty; Alan Valaperti; Corinne Berthonneche; Thierry Pedrazzini; Christoph T Berger; Stephan Dirnhofer; Christian M Matter; Josef M Penninger; Thomas F Lüscher; Urs Eriksson Journal: Circ Res Date: 2009-09-17 Impact factor: 17.367
Authors: Ilonka Rohm; Daniel Kretzschmar; Rudin Pistulli; Marcus Franz; P Christian Schulze; Christian Stumpf; Atilla Yilmaz Journal: J Immunol Res Date: 2016-10-16 Impact factor: 4.818