- Detection of interferon alpha protein reveals differential levels and cellular sources in disease
Rodero et al. report the direct quantification of IFNα protein in monogenic interferonopathies, autoimmunity, and infectious disease states, made possible by the combination of digital ELISA and high-affinity autoantibodies isolated from APECED patients, revealing differential levels and cellular sources dependent on underlying pathology.
- Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs
Ma and colleagues identify CXXC5 as an epigenetic regulator required for maintaining the hypomethylation of a subset of CGIs, thereby promoting the expression of transcriptional factors such as IRF7 in pDCs to enable robust IFN response to viral infection.
- AAV-mediated expression of anti-tau scFvs decreases tau accumulation in a mouse model of tauopathy
Ising et al. report expression of anti-tau scFvs in the brain of a mouse model of tauopathy by AAV-mediated gene transfer. Treated mice show markedly decreased tau hyperphosphorylation and detergent-soluble tau species. Therefore, the Fc domain is not required to mediate effects in tauopathy.
- Optic nerve astrocyte reactivity protects function in experimental glaucoma and other nerve injuries
Sun et al. demonstrate that STAT3 signaling is important for reactive astrocyte remodeling within the injured optic nerve head. Importantly, this reactivity preserves visual function after various optic nerve injuries, including experimental glaucoma.
- Decreased cohesin in the brain leads to defective synapse development and anxiety-related behavior
Cohesin is associated with the developmental disorder Cornelia de Lange syndrome. Fujita et al. show that low levels of cohesin expression in the developing brain result in changes in gene expression that in turn lead to a specific and abnormal neuronal and behavioral phenotype.
- NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia and astrocytes
Lysophosphatidylcholine is associated with neurodegeneration and demyelination. Freeman et al. demonstrate that lysophosphatidylcholine triggers NLRP3- and NLRC4-dependent inflammasome activation, and in a synergistic fashion, NLRP3 and NLRC4 contribute to a cuprizone-induced demyelination model in vivo.
- Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1
Fu et al. demonstrate that reactive oxygen species (ROS)–sensing molecule misshapen/NIK-related kinase 1 (MINK1) can specifically suppress Th 17 cell differentiation through direct phosphorylation of SMAD2. This study provides the mechanism of how ROS limit inflammatory response and unveils the potential health risk of antioxidant supplementation.
- TLR sensing of bacterial spore-associated RNA triggers host immune responses with detrimental effects
Many pathogenic bacterial species produce spores, which may play an important role in their interaction with the host. Choo et al. show that the spores of Bacillus anthracis, the etiologic agent of anthrax, induce type I IFN signaling and disrupt host immune defense via TLR-stimulating RNA.
- In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein
Deeg et al. show a novel line of transgenic mice expressing restriction factor MxA exhibits robust resistance to influenza viruses of avian but not human origin. In vivo evasion of MxA is mediated by distinct amino acids in the nucleoprotein of human influenza viruses.
- DC subset–specific induction of T cell responses upon antigen uptake via Fcγ receptors in vivo
Lehmann et al. targeted antigens to Fcγ receptors expressed on various antigen-presenting cells. Induced CD4+ and CD8+ T cell responses were solely dependent on CD11b+ and CD8+ DC subsets, respectively, but independent of receptor intrinsic ITAM or ITIM signaling domains.