Activation of dendritic cells through the interleukin 1 receptor 1 is critical for the induction of autoimmune myocarditis

U Eriksson, MO Kurrer, I Sonderegger, G Iezzi… - The Journal of …, 2003 - rupress.org
U Eriksson, MO Kurrer, I Sonderegger, G Iezzi, A Tafuri, L Hunziker, S Suzuki, K Bachmaier
The Journal of experimental medicine, 2003rupress.org
Dilated cardiomyopathy, resulting from myocarditis, is the most common cause of heart
failure in young patients. We here show that interleukin (IL)-1 receptor type 1–deficient (IL-
1R1−/−) mice are protected from development of autoimmune myocarditis after
immunization with α-myosin-peptide (614–629). CD4+ T cells from immunized IL-1R1−/−
mice proliferated poorly and failed to transfer disease after injection into naive severe
combined immunodeficiency (SCID) mice. In vitro stimulation experiments suggested that …
Dilated cardiomyopathy, resulting from myocarditis, is the most common cause of heart failure in young patients. We here show that interleukin (IL)-1 receptor type 1–deficient (IL-1R1−/−) mice are protected from development of autoimmune myocarditis after immunization with α-myosin-peptide(614–629). CD4+ T cells from immunized IL-1R1−/− mice proliferated poorly and failed to transfer disease after injection into naive severe combined immunodeficiency (SCID) mice. In vitro stimulation experiments suggested that the function of IL-1R1−/−CD4+ T cells was not intrinsically defect, but their activation by dendritic cells was impaired in IL-1R1−/− mice. Accordingly, production of tumor necrosis factor (TNF)-α, IL-1, IL-6, and IL-12p70 was reduced in dendritic cells lacking the IL-1 receptor type 1. In fact, injection of immature, antigen-loaded IL-1R1+/+ but not IL-1R1−/− dendritic cells into IL-1R1−/− mice fully restored disease susceptibility by rendering IL-1R1−/− CD4+ T cells pathogenic. Thus, IL-1R1 triggering is required for efficient activation of dendritic cells, which is in turn a prerequisite for induction of autoreactive CD4+ T cells and autoimmunity.
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