Genetic defects in the transcription factor forkhead box protein P3 (Foxp3) cause immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX). IPEX is thought to be due to a defect in naturally arising CD4+ Tregs. In this issue of the JCI, Bacchetta and colleagues demonstrate that patients with IPEX and missense mutations in Foxp3 provide insight into the role of various domains of F...

Thromboinflammatory diseases result from the interactions of vascular endothelial cells, inflammatory cells, and platelets with cellular adhesion molecules, plasma proteins, and lipids. Tipping the balance toward a prothrombotic, proinflammatory phenotype results from multicellular activation signals. In this issue of the JCI, Li et al. explore the regulation of heterotypic neutrophil-platelet ...

The transport of heme across membranes is critical for iron absorption, the formation of hemoglobin and other hemoproteins, and iron recycling in macrophages. However, the identity of heme transport proteins has been elusive. In this issue of the JCI, Chiabrando et al. reveal that an isoform of the feline leukemia virus subgroup C receptor (FLVCR1) exports heme from the mitochondria and is crit...

The genetic basis for the attenuation of polio vaccines has been known since the 1980s. Changes in the internal ribosome entry site, within the 5' noncoding region of genomic RNAs, were presumed to reduce translation in certain target organs, leading to the conclusion that attenuation is mediated at the level of translation. A report in this issue of the JCI reveals that poliovirus tropism is, ...

Obesity is associated with a state of chronic, low-grade inflammation. Two manuscripts in this issue of the JCI (see the related articles beginning on pages 1796 and 1821) now report that obese adipose tissue is characterized by macrophage infiltration and that these macrophages are an important source of inflammation in this tissue. These studies prompt consideration of new models to include a...

The highly prevalent protozoan Giardia lamblia is an enteropathogen that can be asymptomatic in some individuals, while leading to persistent diarrhea and substantial morbidity in others. In this issue of the JCI, Bartelt et al. describe a mouse model of the disease and investigate the contribution of coincident malnutrition with the development of symptomatic infection. This work in part expla...

Dystroglycan is a prominent cell surface protein that mediates attachment to the extracellular matrix. Although broadly expressed, glycosylated dystroglycan is critically important for muscle cell adherence to its surrounding matrix. A subgroup of muscular dystrophies, which often manifest in infancy, is associated with reduced glycosylation of dystroglycan. In this issue of the JCI, Beedle et ...

A potent antigen-specific T cell response to HIV infection can contribute to the control of viral replication and is therefore beneficial to the host. However, HIV-mediated increases in generalized T cell activation also appear to accelerate both viral replication and CD4+ T cell depletion. A new study in the JCI attempts to experimentally distinguish the beneficial versus harmful aspects of th...

Recent studies involving molecular modification of adult somatic cells have pointed to a remarkable plasticity in cell identity. In this issue of the JCI, Koh and colleagues assessed whether bone marrow-derived cells could alter their fate under circumstances conducive to adipocyte generation in vivo (see the related article beginning on page 3684). These cells remained true to their roots, ind...

Solid tumor growth requires the formation of new blood vessels to supply nutrients and oxygen to the malignant cells; one approach to cancer therapy is to block this process by inhibiting VEGF signaling. In this issue of the JCI, Pasula et al. demonstrate a surprising role of epsins--proteins involved in endocytosis--in tumor angiogenesis via their modulation of VEGF signaling. Their findings s...