September 2013 | Volume 210, No. 10
Brief Definitive Reports
- The Nlrp3 inflammasome regulates acute graft-versus-host disease
Conditioning therapies before transplantation induce the release of uric acid, which triggers the NLRP3 inflammasome and IL-1β production contributing to graft-versus-host disease.
- Negative selection, not receptor editing, is a physiological response of autoreactive thymocytes
Using a novel physiological knock-in model, direct evidence for self-antigen–induced TCR editing is not observed, but rather autoreactive cells are exclusively eliminated by negative selection.
- CD4+ T cells are trigger and target of the glucocorticoid response that prevents lethal immunopathology in toxoplasma infection
CD4+ T cells regulate their own activity during toxoplasma infection by driving a glucocorticoid response, which results in feedback inhibition of Th1 cytokine production.
- Respiratory virus–induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium
Inhibition of epidermal growth factor receptor during viral infection augments IRF1-dependent IFN-λ production and decreases viral titers.
- Inhibition of the p110α isoform of PI 3-kinase stimulates nonfunctional tumor angiogenesis
Inactivation of the stromal p110α isoform of PI3K increases vascular density, reduces vessel size, and alters pericyte coverage, which results in enhanced tumor hypoxia and necrosis to reduce tumor growth.
- Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the expression of DC-STAMP
The co-repressor Strawberry notch homolog 2 regulates DC-STAMP expression and osteoclast fusion, and its absence results in osteopetrosis.
- Retinoic acid controls the homeostasis of pre-cDC–derived splenic and intestinal dendritic cells
Retinoic acid is required to maintain pre-DC–derived CD11b+CD8α−Esamhigh dendritic cells (DCs) in the spleen and CD11b+CD103+ DCs in the gut.
- Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF
Alveolar macrophages differentiate from fetal monocytes in a GM-CSF–dependent fashion and colonize the alveolar space within a few days after birth.
- VEGF controls lung Th2 inflammation via the miR-1–Mpl (myeloproliferative leukemia virus oncogene)–P-selectin axis
VEGF dampens the expression of microRNA-1, which drives inflammation in part via increasing the expression of Mpl.
- Intestinal lamina propria dendritic cells maintain T cell homeostasis but do not affect commensalism
Targeted deletion of CD103+CD11b+ LP DCs results in reduced LP Th17 cells at steady state, but has no impact on Citrobacter infection or the composition of the intestinal microbiota.
- Intestinal monocytes and macrophages are required for T cell polarization in response to Citrobacter rodentium
Using a new mouse model, the specific deletion of monocytes and macrophages reveals that, although not required to initiate immunity to Citrobacter rodentium, they contribute to the adaptive response via IL-12 secretion to induced IFN-γ+ Th1 polarization.
- ER stress transcription factor Xbp1 suppresses intestinal tumorigenesis and directs intestinal stem cells
X-box–binding protein 1 suppresses tumor formation in the gut by regulating Ire1α and Stat3-mediated regenerative responses in the epithelium as a consequence of ER stress.
- p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells
p53 induction regulates NK cell recruitment via CCL2, leading to NKG2D-dependent elimination of senescent tumors.
- A Toxoplasma dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation
Toxoplasma gondii secretes a novel dense granule protein, GRA24, that traffics from the vacuole to the host cell nucleus where it prolongs p38a activation and correlates with proinflammatory cytokine production.
- Neuroprotective intervention by interferon-γ blockade prevents CD8+ T cell–mediated dendrite and synapse loss
IFN-γ produced by CD8+ cytotoxic T cells acts on neurons to induce Stat1-associated loss of dendrites and synapses in a mouse model of viral encephalitis.
- Epidermal IL-15Rα acts as an endogenous antagonist of psoriasiform inflammation in mouse and man
Epidermal IL-15Rα, shed by keratinocytes upon stimulation with inflammatory cytokines, counteracts IL-15–induced proliferation of IL-17–producing T cells to dampen psoriatic skin disease.
- Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells
T cells from RA patients are hypoglycolytic due to insufficient induction of the glycolytic activator PFKFB3, resulting in impaired autophagy and reduced ROS production.
- Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation, and immunological memory
Targeting antigen to B cells and dendritic cells via direct conjugation to anti-CD180 antibody promotes robust antigen-specific antibody responses in the absence of adjuvant.