July 2016 | Volume 213, No. 8
- Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence?
Stanley and colleagues explore whether changes in insulin levels and insulin signaling are a cause or consequence of AD.
Brief Definitive Reports
- CD6 modulates thymocyte selection and peripheral T cell homeostasis
Orta-Mascaró, Lozano, and collaborators provide the first analysis of CD6-deficient mice, showing that this molecule modulates T cell receptor signaling and the threshold for thymocyte and peripheral T cell subset selection.
- TNF activation of NF-κB is essential for development of single-positive thymocytes
Seddon and colleagues study mice whose T cells lack both of the catalytic subunits of the IKK complex and show that impaired TNF receptor activation of NF-κB is responsible for their block in thymocyte development.
- Critical role of fatty acid metabolism in ILC2-mediated barrier protection during malnutrition and helminth infection
Belkaid et al. show that type 2 innate lymphoid cells rely predominately on fatty acid metabolism during helminth infection and malnutrition.
- Protection against malaria in mice is induced by blood stage–arresting histamine-releasing factor (HRF)–deficient parasites
Mécheri and collaborators generate a Plasmodium strain with a deleted histamine-releasing factor gene that elicits effective cross-strain protection.
- Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects
Somech and colleagues identify two new mutations in STN1 that causes Coats plus syndrome and telomere abnormalities in human, recapitulated in a zebra fish model.
- Identification of embryonic precursor cells that differentiate into thymic epithelial cells expressing autoimmune regulator
mTEC progenitors differentiate to mature Aire+ mTECs through a pathway that initiates with RANK and LtβR signaling via the nonclassical NF-κB, followed by TRAF-6–driven maturation.
- The loss of Ezh2 drives the pathogenesis of myelofibrosis and sensitizes tumor-initiating cells to bromodomain inhibition
Loss of Ezh2 in the presence of activating mutation in JAK2 (JAK2V617F) cooperatively alters transcriptional programs of hematopoiesis, activates specific oncogenes, and promotes the development of myelofibrosis.
- Loss of Ezh2 synergizes with JAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis
Skoda et al. provide new insights into the collaboration between epigenetic regulator Ezh2 and a key hematopoietic tyrosine kinase in disease initiation and progression.
- Developmental regulation of myeloerythroid progenitor function by the Lin28b–let-7–Hmga2 axis
Daley and collaborators show that endogenous Lin28b drives erythroid-dominant fetal hematopoiesis and that decreases in Lin28b activate adult granulocyte-predominant hematopoiesis.
- Genetically distinct leukemic stem cells in human CD34− acute myeloid leukemia are arrested at a hemopoietic precursor-like stage
Quek and colleagues identify human leukemic stem cells (LSCs) present in CD34− AML. In-depth characterization of the functional and clonal aspects of CD34− LSCs indicates that most are similar to myeloid precursors.
- BAFF-secreting neutrophils drive plasma cell responses during emergency granulopoiesis
Harris and collaborators show that neutropenia results in increased formation of plasma cells and elevated antibody production.
- E3 ubiquitin ligase Cbl-b negatively regulates C-type lectin receptor–mediated antifungal innate immunity
Innate immune responses mediated by C-type lectin receptors Dectin-2 and Dectin-3 against fungal infections are negatively regulated by Cbl-b ubiquitination.
- Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection
During viral infections, brain tissue–resident memory T cells (bTRM) prevent fatal brain infection after acquiring perforin- and IFN-γ–dependent effector functions through a pathway that involves presentation of cognate antigen on MHC-I.
- Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4+ T cells into distinct effector subsets
Tangye and collaborators use a series of mutants to elucidate the pathways required to generate distinct subsets of human effector CD4+ T cells.
- Micro–adhesion rings surrounding TCR microclusters are essential for T cell activation
Saito et al. describe a ring of focal adhesion molecules that surrounds T cell receptor microclusters and is essential for early T cell activation.
- Siglec-H protects from virus-triggered severe systemic autoimmunity
Siglec-H is a key negative regulator of the type I interferon pathway, reducing the incidence of autoimmunity after viral infection.