Three muscle-specific microRNAs, miR-206, -1, and -133, are induced during differentiation of C2C12 myoblasts in vitro. Transfection of miR-206 promotes differentiation despite the presence of serum, whereas inhibition of the microRNA by antisense oligonucleotide inhibits cell cycle withdrawal and differentiation, which are normally induced by serum deprivation. Among the many mRNAs that are down-regulated by miR-206, the p180 subunit of DNA polymerase α and three other genes are shown to be direct targets. Down-regulation of the polymerase inhibits DNA synthesis, an important component of the differentiation program. The direct targets are decreased by mRNA cleavage that is dependent on predicted microRNA target sites. Unlike small interfering RNA–directed cleavage, however, the 5′ ends of the cleavage fragments are distributed and not confined to the target sites, suggesting involvement of exonucleases in the degradation process. In addition, inhibitors of myogenic transcription factors, Id1-3 and MyoR, are decreased upon miR-206 introduction, suggesting the presence of additional mechanisms by which microRNAs enforce the differentiation program.

Atopic dermatitis (AD), a chronic relapsing inflammatory skin disease, is increasing in prevalence around the world. Intensive research is ongoing to understand the mechanisms involved in the development of AD and offer new treatment options for patients suffering from AD. In this review, we highlight the importance of allergic Th2 responses in the development of the disease and summarize relevant literature, including genetic studies, studies of human skin and mechanistic studies on keratinocytes and mouse models of AD. We discuss the importance of the skin barrier and review recent findings on the pro-Th2 cytokines TSLP, IL-25, and IL-33, notably their ability to polarize dendritic cells and promote Th2 responses. After a brief update on the contribution of different T-cell subsets to AD, we focus on Th2 cells and the respective contributions of each of the Th2 cytokines (IL-4, IL-13, IL-5, IL-31, and IL-10) to AD. We conclude with a brief discussion of the current gaps in our knowledge and technical limitations.

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The repair protein trefoil factor 2 promotes Th2 responses to helminth infection and allergens in part by inducing IL-33.

Background Exposure to traffic pollution particulate matter, predominantly diesel exhaust particles (DEP), increases risk for asthma and asthma exacerbation, however the underlying mechanisms remain poorly understood. Objective To examine the impact of DEP exposure on the generation and persistence of allergen-specific memory T-cells in asthma and translate these findings by determining the impact of early DEP exposure on the prevalence of allergic asthma in children. Methods The impact of DEP on HDM-specific memory responses was determined using an asthma model. Data from children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort were analyzed to determine the impact of the DEP exposure on asthma outcomes. Results DEP co-exposure with HDM resulted in persistent Th2/Th17 CD127+ effector/memory cells in the lungs, spleen and lymph nodes of adult and neonatal mice. After 7 weeks of rest, a single exposure to HDM resulted in airway hyperresponsiveness and increased levels of Th2 cytokines in only mice that had been previously exposed to both HDM and DEP versus HDM alone. Based on these data, we examined whether DEP exposure was similarly associated increased asthma prevalence in children in the presence or absence of allergen exposure/sensitization in the CCAAPS birth cohort. Early life exposure to high DEP was associated with significantly increased asthma prevalence among allergic children, but not among non-allergic children. Conclusion These findings suggest that DEP exposure results in accumulation of allergen specific Th2/Th17 cells in the lungs, potentiating secondary allergen recall responses and promoting the development of allergic asthma.