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Editors' Picks

        Looking into the hair follicle

        Although stem cells and their progeny are essential for tissue regeneration, the events necessary for regeneration are not fully understood. Because only static and/or invasive methods have been used to investigate these events, in vivo temporal and spatial data on tissue regeneration are lacking. Using a novel noninvasive technique involving two-photon laser scanning microscopy, Rompolas and colleagues examined hair follicle (HF) regeneration over time in live 3-week-old mice. During early regeneration, proliferation was first initiated in the stem cell progeny in the lower portion of the follicle at the interface between the progeny and the mesenchyme, although the stem cells remained quiescent. HFs were observed to rapidly stretch downward during the growth phase, and cell migratory events were observed in the bulge, revealing a previously unidentified growth mechanism. Furthermore, these studies demonstrated that the mesenchymal dermal papilla is required for hair growth initiation. These novel studies offer insight into the dynamic cellular processes of stem cells and their progeny during HF regeneration. (Nature 487:496–9, 2012) Selected by M. Amagai

        Go for the gold

        Topical delivery is optimal for treating skin diseases, and targeted gene suppression by antisense DNA and small interfering RNAs (siRNAs) has shown promising results for a variety of diseases, including cancers and genetic disorders. Zheng and colleagues previously combined these desirable traits and introduced spherical nucleic acid nanoparticle conjugates (SNA-NCs), which are inorganic gold particles densely coated with highly oriented oligonucleotides and are capable of simultaneous transfection and gene regulation. Recently, these investigators demonstrated that SNA-NCs are good candidates for topical delivery due not only to their high transfection efficiency but also to the lack of cellular toxicity and minimal cellular effects in cultured cells. Because epidermal growth factor receptor (EGFR) signaling is important in epidermal cell proliferation and cancers, SNA-NCs were used to knock down EGFR expression in mouse skin and human skin models with minimal off-target effects. These SNA-NCs offer remarkable potential for treating skin diseases, and the versatility of siRNAs may allow for personalized, genotype-based therapies. (Proc Natl Acad Sci USA 109:11975–80, 2012) Selected by L. Goldsmith

        Listen carefully

        Cochlear implantation is useful for treating children with profound hearing loss, but significant limitations still exist. Therefore, interest in restoring organ of Corti function remains high. To facilitate functional restoration of inner hair cells of the cochlea, Akil and colleagues used adeno-associated virus type 1 with a corrected form of the vesicular glutamate transporter-3 (VGLUT-3), which is mutated in one form of hereditary deafness. Following viral delivery of wild-type VGLUT3 to VGLUT3 knockout mice at P10–12, the auditory brainstem response (ABR) threshold normalized within 7–14 days, remained in this range for at least 7 weeks, and in two mice even persisted for 18 months. Earlier delivery at P1–P3 yielded even better inner hair cell transfection and long-lived hearing recovery in these mice. Interestingly, rescue of ABR thresholds was achieved with only a partial reversal of synaptic changes in the mice. (Neuron 75:283–93, 2012) Selected by J. Uitto

        IL-23 stands alone

        Spondyloarthropathy comprises a group of rheumatic diseases characterized by primary articular inflammation in the enthesis. Recent work has highlighted IL-23 as a key player in these diseases because polymorphisms in IL-23 receptor (IL-23R) have been associated with ankylosing spondylitis and HLA-B27, which is present in 90% of these patients and has a tendency to misfold, leading to production of IL-23. Sherlock and colleagues recently discovered a previously unidentified population of IL-23R+ cells in the enthesis. In vivo exposure to IL-23 alone was sufficient to rapidly induce specific entheseal inflammation in mice. The effects of the immunomodulatory IL-23 cytokine are mediated by IL-22 and IL-17. Not surprisingly, IL-22 was found to promote entheseal and periosteal bone formation, indicating that the osteoproliferative component of disease is probably mediated by IL-22. These findings suggest that neutralization of IL-23 pathway components, perhaps IL-17 and IL-22, may ameliorate disease pathology. (Nat Med 18:1069–76, 2012) Selected by J. Uitto

        Unusual cross-reactivity

        Although it is known that environmental factors contribute to autoimmune diseases, the etiology of these diseases remains obscure. Endemic pemphigus foliaceus in Brazil, known as fogo selvagem (FS), is characterized by antidesmoglein 1 (Dsg1) antibodies (IgG4, IgM, and IgE). Exposure to hematophagous insect bites, such as those from sand flies, is a risk factor for FS in Brazil. Qian and colleagues recently demonstrated that IgG4 and IgE autoantibodies from FS sera react with both Dsg1 and the LJM11 antigen from salivary glands of Lutzomyia longipalpis (sand flies). Importantly, sera from mice immunized with LJM11 harbor anti-Dsg1 antibodies. Because no amino acid similarities exist between these cross-reactive antigens, the calcium dependence of the interaction suggests that the autoantibodies react with a conformational epitope. This study provides evidence that a noninfectious environmental agent plays an important role in initiating an autoimmune disease via a mechanism of molecular mimicry. (J Immunol 189:1535–9, 2012) Selected by S. Hwang