The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo

Decay-accelerating factor ([DAF] CD55) is a glycosylphosphatidylinositol-anchored membrane inhibitor of complement with broad clinical relevance. Here, we establish an additional and unexpected role for DAF in the suppression of adaptive immune responses in vivo. In both C57BL/6 and BALB/c mice, deficiency of the Daf1 gene, which encodes the murine homologue of human DAF, significantly enhanced T cell responses to active immunization. This phenotype was characterized by hypersecretion of interferon (IFN)-γ and interleukin (IL)-2, as well as down-regulation of the inhibitory cytokine IL-10 during antigen restimulation of lymphocytes in vitro. Compared with wild-type mice, Daf1−/− mice also displayed markedly exacerbated disease progression and pathology in a T cell–dependent experimental autoimmune encephalomyelitis (EAE) model. However, disabling the complement system in Daf1−/− mice normalized T cell secretion of IFN-γ and IL-2 and attenuated disease severity in the EAE model. These findings establish a critical link between complement and T cell immunity and have implications for the role of DAF and complement in organ transplantation, tumor evasion, and vaccine development

Prion-like Aggregation of Mitochondrial Antiviral Signaling Protein in Lupus Patients Is Associated With Increased Levels of Type I Interferon: MAVS AGGREGATION AND TYPE I IFN IN LUPUS

Increased levels of Type I interferon (IFN-I) and IFN-I-regulated genes are found in patients with systemic lupus erythematosus (SLE) and may be central to its pathogenesis. The mitochondrial adaptor protein MAVS is a key regulator of IFN-I that undergoes a dramatic prion-like aggregation and self-propagates the activation signal from viral RNA to amplify downstream IFN production. We wondered if such MAVS aggregates might play a role in the sustained increased production of IFN-I in SLE

Simulation eines MOSFET-Transistors mit dem Gummel-Algorithmus

SIGLETIB Hannover: RO 6083(1) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman