ON THE COVER
Histological analysis of germinal centers at day 7 after NP-KLH immunization from the paper by Wöhner et al. Cryosections of the spleen were stained with anti-GL7 (blue) and anti-IgD (red) antibodies.
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Live cell imaging to understand monocyte, macrophage, and dendritic cell function in atherosclerosis
Ley et al. provide a review of the technology and accomplishments of dynamic imaging of myeloid cells in atherosclerosis.
Brief Definitive Report
Combined IL-21–primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient
Chapuis et al. demonstrate that the combination of adoptive cellular therapy with CTLA4 blockade induces long-term remission in a melanoma patient resistant to both modalities administered serially and individually.
Identification and treatment of the Staphylococcus aureus reservoir in vivo
Kubes et al. show that methicillin-resistant Staphylococcus aureus (MRSA) survive and proliferate inside Kupffer cells. Intracellular MRSA is resistant to neutrophil-killing and antibiotics treatment and, when released into the circulation, can infect other organs.
G9a regulates group 2 innate lymphoid cell development by repressing the group 3 innate lymphoid cell program
Antignano, Zaph, and collaborators show that the lysine methyltransferase G9a plays a critical role in determining the developmental programs of group 2 and 3 innate lymphoid cells.
Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome
Meuwissen and collaborators define a novel genetic cause of pseudo-TORCH syndrome, which resembles the sequelae of congenital infection and represents a novel type I interferonopathy.
Developmental regression of hyaloid vasculature is triggered by neurons
Kubota and colleagues show that neurons sequester VEGF to prune blood vessels during eye development.
Early onset combined immunodeficiency and autoimmunity in patients with loss-of-function mutation in LAT
Keller et al. describe for the first time human LAT deficiency, which causes severe immune dysregulation with autoimmunity, lymphoproliferation, and progressive immunodeficiency.
Molecular functions of the transcription factors E2A and E2-2 in controlling germinal center B cell and plasma cell development
Busslinger et al. showed that the transcription factors E2A and E2-2 control the expression of genes required for the development of GC B cells and plasma cells.
Gut microbiota translocation to the pancreatic lymph nodes triggers NOD2 activation and contributes to T1D onset
Streptozotocin causes T1D by inducing the translocation of intestinal bacteria into pancreatic lymph nodes and driving the development of pathogenic Th1 and Th17 cells through NOD2 receptor.
Anti-TNF drives regulatory T cell expansion by paradoxically promoting membrane TNF–TNF-RII binding in rheumatoid arthritis
Nguyen and Ehrenstein reveal that anti-TNF antibodies paradoxically enhance membrane TNF–TNF-RII interactions to increase Foxp3 expression and confer upon T reg cells the ability to suppress Th17 cells in rheumatoid arthritis patients.
Clonal redemption of autoantibodies by somatic hypermutation away from self-reactivity during human immunization
Goodnow et al. show that in vaccinated humans, anergic autoreactive B cells can hypermutate the B cell receptor during the immune response and remove binding to self while enhancing binding to the vaccine.
Increased expression of AT-1/SLC33A1 causes an autistic-like phenotype in mice by affecting dendritic branching and spine formation
Increased expression of the ER membrane acetyl-CoA transporter AT-1 can cause an autism-like phenotype in mice.
Targeting MTHFD2 in acute myeloid leukemia
Pikman et al. demonstrate that the mitochondrial enzyme MTHFD2 is a potential therapeutic target in acute myeloid leukemia.
Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone
Human babesiosis is a tick-borne multisystem disease, and current treatments have both adverse side effects and a significant rate of drug failure. Lawres et al. report that endochin-like quinolones, in combination with atovaquone, cure experimental babesiosis in immunodeficient mice.
IL-4 sensitivity shapes the peripheral CD8+ T cell pool and response to infection
Homeostatic levels of IL-4 are necessary for normal development of memory phenotype CD8+ T cells and naive CD8+ T cells and for a robust CD8+ T cell response to LCMV infection.
Human T cell responses to Japanese encephalitis virus in health and disease
Healthy donors exposed to Japanese encephalitis (JE) virus show a CD8+ T cell response that cross reacts with other flaviviruses. Patients that recovered from JE show a CD4+ T cell response that targets structural proteins of JE virus.
Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction
Ngkelo et al. use a mast cell–deficient mouse model to reveal a protective role of mast cells in myocardial infarction, through regulation of the cardiac contractile machinery.