August 2014 | Volume 211, No. 9
Brief Definitive Reports
- Long-term survival of influenza virus infected club cells drives immunopathology
Club cells are infected by influenza virus, survive acute infection, and establish a proinflammatory environment that contributes to lung pathology. Depletion of club cells reduces lung tissue damage associated with flu infection.
- RHEX, a novel regulator of human erythroid progenitor cell expansion and erythroblast development
RHEX is a novel target of the human erythropoietin receptor, and modulator of EPO-dependent red cell production.
- Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens
Nfil3 is critical for normal development of innate lymphoid cell (ILC) progenitors. Nfil3-deficient mice have severely reduced lung and visceral adipose tissue ILC2s and gut-associated ILC3s, and compromised innate immunity to acute bacterial infection.
- Nfil3 is required for the development of all innate lymphoid cell subsets
Loss of Nfil3 selectively reduces Peyer’s patch formation, impairing recruitment and distribution of lymphocytes and compromising immune responses to inflammatory and infectious agents.
- The small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation
Mice lacking the small GTPase Rap1b exhibit enhanced neutrophil recruitment to inflamed lungs and susceptibility to endotoxin shock via enhance PI3K-Akt activation.
- Tight regulation of ubiquitin-mediated DNA damage response by USP3 preserves the functional integrity of hematopoietic stem cells
In vivo deletion of USP3, a deubiquitinating enzyme involved in DNA damage repair, increases the incidence of spontaneous cancer and impairs the proliferation and repopulation ability of HSCs.
- Targeting PI3Kγ activity decreases vascular trauma-induced intimal hyperplasia through modulation of the Th1 response
PI3Kγ plays a major role in the initiation and progression of intimal hyperplasia by specifically modulating Th1 cytokines leading to CXCL10 and RANTES production by smooth muscle cells.
- Dissecting the complement pathway in hepatic injury and regeneration with a novel protective strategy
A novel site-targeted murine complement inhibitor, CR2-CD59, specifically inhibits the terminal membrane attack complex. This inhibitor dissects the complement pathway to protect against liver injury while promoting regeneration in mouse models of liver resection and acute liver failure.
- Role of Blimp-1 in programing Th effector cells into IL-10 producers
The transcriptional regulator Blimp-1 is absolutely required for IL-10 production in Th1 cells and limits inflammatory effector T cell responses downstream of IL-12 and IL-27.
- RUNX1-dependent RAG1 deposition instigates human TCR-δ locus rearrangement
Within the human TCR-α/δ locus, ordered rearrangements requires RUNX1, which binds to the Dδ2-23RSS and interacts with RAG1 to enhance RAG1 deposition at this site. Absence of this RUNX1 binding site in the homologous murine Dδ1-23RSS offers an explanation for the lack of ordered TCR-δ gene assembly in mice.
- VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells
Schneider-Hohendorf describe expression of adhesion molecules MCAM and PSGL-1 on human CD4+ T cells and Th17 T cells in multiple sclerosis patients under long-term natalizumab treatment. The authors identify that despite blockade of VLA-4, MCAM+ T cells can migrate through the blood–brain barrier to access the CNS through PSGL-1 and MCAM.
- Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease
Immunosuppression from amyloidogenic peptides arises from two pathways, expression of type 1 IFN by pDCs and reduced expression of IFN-γ, TNF, and IL-6, which together modulate the signs of both Th1- and Th17-induced EAE.
- Sox5 and c-Maf cooperatively induce Th17 cell differentiation via RORγt induction as downstream targets of Stat3
A novel isoform of Sox5, Sox5t, and c-Maf activate RORγt to induce Th17 cells. Sox5−/− mice exhibit impaired Th17 differentiation and are thus resistant to EAE and delayed-type hypersensitivity.
- Classical Flt3L-dependent dendritic cells control immunity to protein vaccine
Protective immunity to protein vaccines is controlled by Flt3L-dependent classical LN-resident dendritic cells, and dampened by migratory dendritic cells.
- Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing
An antibody directed against the O-antigen of Pseudomonas aeruginosa LPS can block complement-mediated bacterial killing and contributes to the severity of respiratory infection.
- Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection
T reg cells effectively maintain CD8 T cell exhaustion during chronic LCMV infection, but blockade of PD-1 is critical for elimination of infected cells.