Details

Autor(en) / Beteiligte

• Eriksson, Urs
• Kurrer, Michael O
• Sonderegger, Ivo
• Iezzi, Giandomenica
• Tafuri, Anna
• Hunziker, Lukas
• Suzuki, Shinobu
• Bachmaier, Kurt
• Bingisser, Roland M
• Penninger, Josef M
• Kopf, Manfred

Titel

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

Ist Teil von

• The Journal of experimental medicine, 2003-02, Vol.197 (3), p.323-331

Ort / Verlag

United States: The Rockefeller University Press

Erscheinungsjahr

2003

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 alpha-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)-alpha, 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.