May 2016 | Volume 213, No. 6
Brief Definitive Reports
- NLRP3 recruitment by NLRC4 during Salmonella infection
By engineering a mutant mouse strain that preserves the scaffolding function of NLRC4, Dixit et al. show cooperativity between it and another NOD family sensor, NLRP3.
- Bridging channel dendritic cells induce immunity to transfused red blood cells
Calabro et al. show that 33D1+ dendritic cells present in the bridging channel of the spleen are essential for alloantibody response to transfused red blood cells.
- The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2
Lambrecht et al. show that the transcription factor Zeb2 regulates commitment toward both the pDC and cDC2 lineages by repressing Id2.
- Recent thymic emigrants are tolerized in the absence of inflammation
CD4+ and CD8+ recent thymic emigrants (RTEs) exhibit an anergic phenotype after encounter with self-antigen in the periphery. In the presence of inflammation, both CD4+ and CD8+ RTEs can be converted into competent diabetogenic effector cells.
- Epstein-Barr virus nuclear protein EBNA3C directly induces expression of AID and somatic mutations in B cells
Allday and collaborators demonstrate that the EBV transcription factor and oncoprotein EBNA3C directly induces the expression of AID and somatic mutations in B cells, providing a mechanism linking infection and lymphoma induction.
- Myeloid cell transmigration across the CNS vasculature triggers IL-1β–driven neuroinflammation during autoimmune encephalomyelitis in mice
Work in a mouse model suggests that central inhibition of IL-1β/IL-1R1 signaling during the early acute phase of neuroinflammation may be an effective means for preventing loss of neurological function in multiple sclerosis.
- Local antigen in nonlymphoid tissue promotes resident memory CD8+ T cell formation during viral infection
CD8+ T cells activated during viral infection migrate to infected skin in an antigen-independent manner. Local recognition of antigens drives the differentiation into Trm CD8+ T cells.
- Class-switched anti-insulin antibodies originate from unconventional antigen presentation in multiple lymphoid sites
Unanue and colleagues show that activation of anti-insulin lymphocytes can occur at diverse anatomical sites in response to circulating insulin and may be driven by unconventional antigen presentation by germinal center B cells.
- Single-cell transcriptional analysis of normal, aberrant, and malignant hematopoiesis in zebrafish
Moore et al. reports the first single-cell gene expression analysis in zebrafish blood to distinguish major blood lineages, identify new cell types, and delineate heterogeneity in T cell leukemia.
- Ubiquitin-mediated fluctuations in MHC class II facilitate efficient germinal center B cell responses
The ubiquitin E3 ligase March1 controls the turnover and surface levels of peptide–MHCII in GC B cells, contributing to optimal GC responses.
- A nonsense mutation in the DNA repair factor Hebo causes mild bone marrow failure and microcephaly
de Villartay et al. describe a patient with a DNA repair factor mutation that leads to an increased sensitivity to DNA-damaging agents and, ultimately, to mild bone marrow failure and microcephaly.
- Ubiquitin E3 ligase FIEL1 regulates fibrotic lung injury through SUMO-E3 ligase PIAS4
Lear et al. report a novel molecular pathway in which Fibrosis Inducing E3 Ligase 1 (FIEL1) regulates TGFβ and fibrosis pathway through SUMO-E3 ligase PIAS4. They also develop a small molecule inhibitor toward FIEL1 that is highly effective in ameliorating fibrosis in mice.
- A neuroprotective role for microglia in prion diseases
Microglial activation is a hallmark of most neurodegenerative disorders, yet it is not clear if it plays beneficial or deleterious roles. Zhu et al. provide evidence for a general protective role of microglia in the pathogenesis of prion diseases.
- Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever
Work in humans and mice highlights the role of tryptophan metabolism in the immunopathogenesis of typhoid fever, offering novel insight into clinical disease.
- Interferon-γ facilitates hepatic antiviral T cell retention for the maintenance of liver-induced systemic tolerance
IFN-γ mediates hepatic T cell retention and the maintenance of systemic tolerance during hepatitis B virus persistence in the liver.
- Dynamic changes in Id3 and E-protein activity orchestrate germinal center and plasma cell development
Gloury et al. reveal an essential role for the Id3–E-protein axis in the transcriptional regulation of humoral immunity.