SPATA2 restricts OTULIN-dependent LUBAC activity independently of CYLD.

SPATA2 mediates the recruitment of CYLD to immune receptor complexes by bridging the interaction of CYLD with the linear ubiquitylation assembly complex (LUBAC) component HOIP. Whether SPATA2 exhibits functions independently of CYLD is unclear. Here, we show that, while Cyld and Spata2 mice are viable, double mutants exhibit highly penetrant perinatal lethality, indicating independent functions of SPATA2 and CYLD.

Therapeutic effects of Fc gamma RIV inhibition are mediated by selectively blocking immune complex-induced neutrophil activation in epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is a subepidermal autoimmune bullous disease caused by autoantibodies targeting type VII collagen (COL7). It is characterized by inflammation and subepidermal blistering mainly through immune complex (IC)-mediated activation of neutrophils. In experimental EBA, binding of neutrophils to ICs in the skin and induction of clinical disease depends on the expression of the Fc gamma receptor (FcγR) IV.

Keeping Cell Death in Check: Ubiquitylation-Dependent Control of TNFR1 and TLR Signaling.

Pro-inflammatory signaling pathways, induced by pathogens, tissue damage or cytokines, depend on the ubiquitylation of various subunits of receptor signaling complexes, controlled by ubiquitin ligases and deubiquitinases. Ubiquitylation sets the stage for the activation of kinases within these receptor complexes, which ultimately regulate pro-inflammatory gene expression. The receptors, which transduce pro-inflammatory signals, can often induce cell death, which is controlled by ubiquitylation as well.