Complement regulation leads to the generation of complement split products such as complement component (C)4d, a marker for disease activity in autoimmune syndromes or antibody-mediated allograft rejection. However, the physiologic role of C4d has been unknown. The present study identifies Ig-like transcript (ILT)4 and ILT5v2 as cellular receptors for C4d.
Both receptors, expressed on monocytes, macrophages and dendritic cells, also interacted with complement split products C3d, C4b, C3b and iC3b. However, C4d did not bind to classic complement receptors. In monocytes, C4d exerted a dose-dependent inhibition of pro-inflammatory cytokine secretion as well as an attenuation of intracellular Ca2+ flux. Cell surface-resident ILT4 conferred endocytosis of soluble monomeric C4d.
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