November 2016 | Volume 213, No. 12
- Type I interferon–mediated monogenic autoinflammation: The type I interferonopathies, a conceptual overview
In this review paper, Rodero and Crow outline the current understanding of the type I interferonopathies.
Brief Definitive Reports
- Interferon lambda 4 expression is suppressed by the host during viral infection
Hong et al. show that IFNλ4 exhibits similar antiviral activity to IFNλ3. Humans deploy several mechanisms to limit expression of functional IFNλ4 through noncoding splice variants and nonfunctional protein isoforms.
- Mafb lineage tracing to distinguish macrophages from other immune lineages reveals dual identity of Langerhans cells
Using Mafb-driven Cre, Murphy et al. establish a new tool to discriminate macrophages from other myeloid cells in vivo.
- Adrenergic control of the adaptive immune response by diurnal lymphocyte recirculation through lymph nodes
Suzuki et al. show that neural inputs to β2-adrenergic receptors expressed on lymphocytes generate the diurnal variation in the frequency of lymphocyte egress from lymph nodes, which is reflected in the magnitude of the adaptive immune response.
- Single-cell imaging of normal and malignant cell engraftment into optically clear prkdc-null SCID zebrafish
Moore and colleagues present new strains of optically clear immune-deficient zebrafish that allow for dynamic imaging of regeneration and tumor progression at single-cell resolution in live animals.
- In vivo conditional deletion of HDAC7 reveals its requirement to establish proper B lymphocyte identity and development
The histone deacetylase HDAC7 interacts with and represses myeloid and T cell genes in pro–B cells. HDAC7 deletion blocks early B cell development and results in severe lymphopenia.
- Gut dysbiosis impairs recovery after spinal cord injury
Kigerl et al. show that spinal cord injury causes profound changes in gut microbiota and that these changes in gut ecology are associated with activation of GALT immune cells. They show that feeding mice probiotics after SCI confers neuroprotection and improves functional recovery.
- High-dimensional single-cell analysis reveals the immune signature of narcolepsy
Hartmann et al. show that, in narcolepsy, T cells exhibit a proinflammatory signature characterized by increased production of TNF, IL-2, and B cell–supporting cytokines.
- Unique pathological tau conformers from Alzheimer’s brains transmit tau pathology in nontransgenic mice
Intracerebral inoculation of tau fibrils from AD brains results in the induction and propagation of tau inclusions in WT mice.
- Potential biomarkers to follow the progression and treatment response of Huntington’s disease
Disatnik et al. identify mitochondrial DNA levels, 8-OHdG, and inflammation factors as potential peripheral biomarkers to follow progression and treatment response of Huntington’s disease.
- LUBAC deficiency perturbs TLR3 signaling to cause immunodeficiency and autoinflammation
LUBAC components interact with the TLR3 signaling cascade at different levels, thereby tightly controlling TLR3-mediated innate immunity.
- CD72 negatively regulates B lymphocyte responses to the lupus-related endogenous toll-like receptor 7 ligand Sm/RNP
Akatsu and colleagues show that CD72 specifically recognizes Sm/RNP, a lupus-related self-antigen and an endogenous TLR7 ligand, and inhibits B cell responses to Sm/RNP. In mice, CD72 prevents production of anti-Sm/RNP antibodies crucial for lupus development.
- Impairment on the lateral mobility induced by structural changes underlies the functional deficiency of the lupus-associated polymorphism FcγRIIB-T232
Xu et al. show that the lupus-associated polymorphism FcγRIIB-T232 has structural changes of the TM domain that reduces lateral mobility and inhibitory functions.
- Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge’s disease
Azad and collaborators propose that Senp1 drives excessive erythropoiesis in high-altitude Andean dwellers suffering from chronic mountain sickness.
- Tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection
Nabekura and Lanier demonstrate that two distinct long-lived NK cell subsets with different functional properties differentiate during mouse model of cytomegalovirus (MCMV) infection. NK cells expressing the MCMV-specific Ly49H receptor differentiated into memory NK cells and Ly49H− NK cells differentiated into cytokine-activated NK cells. Memory NK cells show enhanced effector function, whereas cytokine-activated NK cells persisted better in an MCMV-free environment.
- Scramblase TMEM16F terminates T cell receptor signaling to restrict T cell exhaustion
The scramblase TMEM16F is indispensable for the formation of multivesicular bodies in late endosomes that facilitate TCR degradation and signal termination. Hyperactivation of TMEM16F-deficient T cells in chronic LCMV infection leads to severe T cell exhaustion and uncontrolled virus burden.
- MAIT cells promote inflammatory monocyte differentiation into dendritic cells during pulmonary intracellular infection
Cowley and Meierovics show that mucosa-associated invariant T (MAIT) cells promote the differentiation of monocytes into monocyte-derived dendritic cells during Francisella tularensis LVS pulmonary infection.
- pMHC affinity controls duration of CD8+ T cell–DC interactions and imprints timing of effector differentiation versus expansion
Ozga and colleagues use intravital two-photon microscopy and quantitative whole-organ imaging to reveal the dynamics of early affinity-driven CD8+ T cell activation.