The pathological role of Tenascin-C in the development of myocarditis

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860581
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: University of Tsukuba
• Principal Investigator: TAJIRI Kazuko 筑波大学, 医学医療系, 助教 (60633914)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 心筋炎 / Matricellular蛋白 / テネイシンC / 心筋症 / 樹状細胞

Outline of Final Research Achievements

Tenascin-C (TNC), an extracellular matrix glycoprotein is sparse in the normal adult heart. TNC expresses under pathological conditions, and is closely associated with tissue injury and inflammation. However, the pathophysiological role of TNC in the development of myocarditis is not clear. We examined how TNC affects the initiation of experimental autoimmune myocarditis, immunologically.
We found that TNC-KO mice were protected from severe myocarditis compared to WT mice. TNC induced synthesis of IL-6 in dendritic cells (DCs) via activation of a TLR4, which led to Th17 cell differentiation and exacerbated the myocardial inflammation. In the transfer experiment, DCs loaded with cardiac myosin peptide acquired the functional capacity to induce myocarditis when stimulated with TNC; however, TNC-stimulated DCs generated from TLR4-KO mice did not induce myocarditis in recipients.
Thus, TNC aggravates autoimmune myocarditis by driving the DC activation and Th17 differentiation via TLR4.

Free Research Field

循環器内科学