A bioengineered bilayered living cellular construct promotes ulcer healing by modulating inflammation, stimulating wound edge keratinocytes, and attenuating Wnt/β-catenin signaling to activate an acute wound response.

Objective: Genetic variants of the interferon (IFN) regulatory factor 5 gene (IRF5) are associated with susceptibility to systemic lupus erythematosus (SLE). The contribution of these variants to IRF‐5 expression in primary blood cells of SLE patients has not been addressed, nor has the role of type I IFNs. The aim of this study was to determine the association between increased IRF‐5 expression and the IRF5 risk haplotype in SLE patients.Methods: IRF‐5 transcript and protein levels in 44 Swedish patients with SLE and 16 healthy controls were measured by quantitative real‐time polymerase chain reaction, minigene assay, and flow cytometry. Single‐nucleotide polymorphisms rs2004640, rs10954213, and rs10488631 and the CGGGG insertion/deletion were genotyped in these patients. Genotypes of these polymorphisms defined both a common risk haplotype and a common protective haplotype.Results: IRF‐5 expression and alternative splicing were significantly up‐regulated in SLE patients compared with healthy donors. Enhanced transcript and protein levels were associated with the risk haplotype of IRF5; rs10488631 displayed the only significant independent association that correlated with increased transcription from the noncoding first exon 1C. Minigene experiments demonstrated an important role for rs2004640 and the CGGGG insertion/deletion, along with type I IFNs, in regulating IRF5 expression.Conclusion: This study provides the first formal proof that IRF‐5 expression and alternative splicing are significantly up‐regulated in primary blood cells of patients with SLE. Furthermore, the risk haplotype is associated with enhanced IRF‐5 transcript and protein expression in patients with SLE.

Leukocyte telomere length (LTL), which reflects telomere length in other somatic tissues, is a complex genetic trait. Eleven SNPs have been shown in genome-wide association studies to be associated with LTL at a genome-wide level of significance within cohorts of European ancestry. It has been observed that LTL is longer in African Americans than in Europeans. The underlying reason for this difference is unknown. Here we show that LTL is significantly longer in sub-Saharan Africans than in both Europeans and African Americans. Based on the 11 LTL-associated alleles and genetic data in phase 3 of the 1000 Genomes Project, we show that the shifts in allele frequency within Europe and between Europe and Africa do not fit the pattern expected by neutral genetic drift. Our findings suggest that differences in LTL within Europeans and between Europeans and Africans is influenced by polygenic adaptation and that differences in LTL between Europeans and Africans might explain, in part, ethnic differences in risks for human diseases that have been linked to LTL.