FUNCTIONALLY DISTINCT FORM OF C1Q IN THE REGULATION OF DENDRITIC CELLS AND THE IMPLICATIONS ON SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract

C1q is a protein complex whose hereditary deficiency is associated with the occurrence of Systemic Lupus Erythematosus. In this study an alternative Low Molecular Weight (LMW) form of C1q was found to be secreted by human macrophages and dendritic cells. LMW C1q has an impaired capacity to elicit complement activation and is composed of a distinct subunit structure. LMW C1q differentiated dendritic cells (DCs) have an enhanced propensity to skew towards Th-1 pathway with higher levels of IL-12p70 secretion and decreased IL-10 secretion. LMW C1q DCs have greater potential to induce IFN-¿ positive T cells with parallel T cell proliferation. LMW C1q also impacts on DCs uptake of apoptotic cells and the cytokine milieu in which self antigens are presented. This study strives to understand an alternative dimension of how C1q synthesis in its two forms (Normal/LMW) could affect the pathology of SLE.