Macrophages represent the major pool of IL-7Rα expressing cells in patients with myocarditis. (June 2020) - Kubin, Natalia
Highlights: Myocardial inflammation is initially protective but often leads to heart failure. Main infiltrating cells are macrophages and T cells but B cells are rarely present. Surprisingly, macrophages but not T cells are the major IL-7Rα expressing population. The IL-7Rα cascade is activated and might regulate trafficking of macrophages. Consumption of IL-7 by macrophages might reduce the number of cardiac T and B cells. Abstract: Myocarditis is characterized by infiltration and activation of cytokine as well as chemokine receptors frequently producing heart failure. Causes are often infections triggering inflammatory and immune responses but these initial lines of defense might be finally disastrous. To identify mediators we screened various receptors by confocal microscopy and identified cardiac interleukin-7 (IL-7) receptor-α (IL-7Rα) expressing cells in patients with myocarditis. IL-7Rα + cells were analyzed by markers for leukocytes (CD45), B cells (CD19), T cells (CD3, CD4, CD8) and macrophages (CD68, CD163, CD206). Immune cells were hardly detected in controls. In patients with myocarditis main inflammatory populations consisted of macrophages and T cells. B cells were hardly present. 90% of CD68 + macrophages but less than 20% of CD3 + T cells were IL-7Rα + . This was surprising since T and B lymphocytes are generally regarded as the major IL-7Rα + cells. Since IL-7 acts as a chemokine, the expression of its receptor might orchestrate cardiac macrophage infiltration. In contrast, consumption of IL-7 by IL-7Rα + cardiac macrophages might potentially prevent a certain overshooting immune reaction and sepsis by reducing proliferation and survival of lymphocytes. Our data suggest a participation of IL-7Rα + macrophages in the development of myocarditis and heart failure.