Editors' Picks

        Searching for autoimmunity in AD

        Atopic dermatitis (AD) is increasing worldwide, and environmental factors and allergens have been suggested to play a role in determining disease expression. Although the involvement of immune mechanisms against self-components has been proposed, the role of autoimmunity in AD is unclear. Tang and colleagues recently performed a systematic literature review to evaluate the prevalence and specificity of autoreactivity in AD patients as well as to determine whether clinical disease severity was correlated with autoreactivity. Of the 1,408 studies describing autoimmunity and AD or eczema, 31 were deemed suitable for inclusion in this meta-analysis. In 14 of these studies, autoreactivity was reported in 18–91.4% of 1,253 AD patients and in only 0–11.7% of controls. In AD patients, IgE autoreactivity is a specific phenomenon because no such association was detected in healthy patients or in those with other atopic or inflammatory conditions. Unequivocal determination of the role of autoimmunity in AD is important because such information may lead to new therapies to inhibit the development and progression of autoimmunity; thus, longitudinal studies of this concept are necessary. (J Allergy Clin Immunol 129:1209–15, 2012) Selected by B. Gilchrest

        Commensal calibration

        Previous studies indicated that commensal bacterial communities, which colonize the skin and vaginal, upper respiratory, and gastrointestinal tracts, alter a patient's susceptibility to diabetes, cancer, allergy, and infection, although the mechanisms that underlie this influence remain unknown. Abt and colleagues found that the manipulation of commensal bacteria in antibiotic-treated (ABX) mice resulted in impaired protective immunity in the face of infection with either lymphocyte choriomeningitis virus or influenza virus. Both adaptive and innate antiviral immune responses were affected in these mice. Interestingly, genome-wide transcriptional profiling in combination with functional studies revealed defective expression of antiviral defense genes in macrophages from the ABX mice. Together, these data suggest that signals from commensal bacteria calibrate the activation threshold of the innate antiviral immune response. The findings offer hope that manipulation of bacteria via probiotic treatment or bacteriotherapy will be useful for improving antiviral responses in humans. (Immunity 37:158–70, 2012) Selected by M. Amagai

        Implicate the innate

        Psoriasis relapses have been inadvertently induced in patients and mice by treatment with Aldara, a cream that contains imiquimod. This observation implicates T helper type 17 effector cells in psoriasis. Pantelyushin and colleagues utilized a mouse model to demonstrate that initiation of plaque formation following Aldara treatment is dependent on skin-infiltrating γδ T cells that express the RAR-related orphan receptor gamma (RORγt) transcription factor and on innate lymphoid cells (ILCs). IL-17A, IL-17F, and IL-22 were found to be critical for psoriatic plaque formation, and RORγt+ γδ T cells and ILCs were the predominant producers of these cytokines in this model. The study establishes the sufficiency of a dysregulated innate immune compartment for psoriatic plaque formation. (J Clin Invest 122:2252–6, 2012) Selected by S. Hwang

        Next phase for BCC treatment

        Basal cell carcinoma (BCC), the most common cancer, is typically treated surgically; however, no effective treatment is available for advanced or metastatic disease. Dysregulated hedgehog signaling has been implicated in the pathogenesis of BCC, and vismodegib (GDC-0449, Genentech), a small-molecule inhibitor of this signaling pathway, has shown promise for treatment of advanced BCC in a phase I trial. Sekulic and colleagues recently performed a multicenter, international, nonrandomized study of vismodegib in 96 patients with locally advanced or metastatic BCC. The response rate was 30% in 33 metastatic BCC patients and 43% in 63 locally advanced BCC patients. Unfortunately, 25% of patients reported serious adverse effects, and fatal events were noted in seven cases. Despite these side effects, this phase II trial demonstrated that vismodegib treatment is an effective new treatment for advanced BCC, and it led to the approval of the drug by the US Food and Drug Administration. (N Engl J Med 366:2171–9, 2012) Selected by E. Lerner

        Signal for solar injury

        Exposure to UVB solar radiation evokes an inflammatory reaction of the skin, and this reaction has been characterized by activation of NF-κB and induction of cytokines, including IL-6 and tumor necrosis factor-α (TNF-α), which exerts pleiotropic downstream effects after solar injury. Bernard and colleagues recently found that RNA that is released from keratinocytes upon exposure to UVB radiation stimulates production of TNF-α and IL-6. Using whole-transcriptome shotgun sequencing, these investigators demonstrated that these small nuclear RNAs formed double-stranded RNAs to activate Toll-like receptor 3 (TLR3), which is required for this inflammatory response to UVB. In vivo, UVB-irradiated U1 RNA induced redness and increased ear thickness in mouse ears and increased the expression of TNF-α and IL-6 in wild-type but not TLR3-deficient mice, confirming the role of these RNA molecules in induction of the inflammatory response. Thus, self-RNAs signal UVB solar damage via TLR3, and these results suggest that these molecules may be useful biomarkers or therapy targets for photodamage disorders. (Nat Med, published online 8 July 2012; doi:10.1038/nm.2861) Selected by B. Gilchrest