Activation of Dendritic Cells Through the Interleukin 1 Receptor 1 is Critical for the Induction of Autoimmune Myocarditis

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2003 Feb 5

PMID 12566416

Citations 55

Authors

Urs Eriksson

Michael O Kurrer

Ivo Sonderegger

Giandomenica Iezzi

Anna Tafuri

Lukas Hunziker

Shinobu Suzuki

Kurt Bachmaier

Roland M Bingisser

Josef M Penninger

Manfred Kopf

Affiliations

Soon will be listed here.

Abstract

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.

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