Figure 1.

Impaired clearance of apoptotic cells and/or NETs leads to an enduring exposure of modified histones to the immune system – insufficiently cleared apoptotic cells by macrophages undergo secondary necrosis (SNe), thereby externalizing modified autoantigens such as histones that become recognized as foreign and dangerous by receptors of the innate immune system such as toll-like receptors (TLR). Modified histones are also highly present in NETs, that are also not properly cleared in SLE due to polymorphisms in the DNase I gene (not shown), inhibitory anti-DNase I autoantibodies, or NET-bound proteins such as HMGB1, LL-37, C1q (not shown), and anti-chromatin autoantibodies that prevent the accessibility for DNase I to the NET. The PTMs that are shown are associated with apoptosis (blue), NETosis, or both (green) and are linked to the autoimmune response in SLE.