Visit our Expo - Redox and Inflammation signaling 2012

Signaling pathways controlling self-tolerance: On the road to systemic autoimmune
diseases
Moncef ZOUALI
INSERM U606, Centre Viggo Petersen, Hôpital Lariboisière,
2, rue Ambroise Paré, 75475 Paris Cedex 10, France,
The immune receptors of lymphocytes are able to sense the nature of bound ligands. Through
coupled signaling pathways the generated signals are appropriately delivered to the
intracellular machinery, allowing specific functional responses. A central issue in
contemporary immunology is how the fate of B lymphocytes is determined at the successive
developmental stages and how the B cell receptor distinguishes between signals that induce
immune response or tolerance. Experiments with mice expressing transgenes or lacking
signal transduction molecules are providing important clues to the mechanisms that regulate
signaling thresholds at different developmental stages. Their relevance for the pathogenesis
of autoimmune diseases in clinical settings is currently the focus of interest, particularly since
in some instances, similar defects have been identified in human autoimmune diseases. The
fact that altered signaling has been described in both T cells and B cells of autoimmune
patients strengthens the view that the abnormalities observed are relevant to the pathogenesis.
The studies are also revealing novel potential mechanisms of induction of autoimmunity,
which may have a bearing on the understanding of human diseases.
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