Conflict of interest: MLM developed thymus transplantation intellectual property, which has been licensed to Enzyvant Therapeutics. Both MLM and Duke University may benefit financially if the technology is commercially successful in the future.

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Three of these variants were associated with a significant risk reduction in all 3 variables. Only 2 variants provided similar risk reductions in those who received HN019. CONCLUSIONS. This study found that supplementation with Lactobacillus rhamnosusstrain HN001 could reduce the risk of atopy and eczema development in subjects with TLR genetic variants typically associated with a higher risk of these diseases. REVIEWER COMMENTS. This study highlights the growing interest in the use of probiotics for the prevention and treatment of atopic disorders. Several studies have shown reduction in eczema risk, but the mechanism in which probiotics accomplish this has been unknown. The authors demonstrate the role of probiotic interaction with TLR SNP variants, identifying a novel mechanism through which risk reduction occurs. The study also suggests that this intervention should begin early, during pregnancy, to have significant benefit.

Forkhead Box N1 (FoxN1) is an epithelial-specific transcription factor essential for the development of the thymus. Patients with mutations in Foxn1 (OMIM # 600838) are born with a severe T-cell lymphopenia that presents in combination with alopecia and nail dystrophy. The nude mouse, which developed from a spontaneous genetic mutation in Foxn1, phenocopies the human disease. We report on 3 independently identified patients that presented with low to absent circulating T cells. Genetic workup of these patients revealed mutations in Foxn1. Each patient had distinct compound heterozygous mutations that were localized in the distal exons of Foxn1. These were predicted to maintain Foxn1 expression while adversely affect its function. Of significance, each patient had normal hair and skin, without any evidence of nail dystrophy, distinct from previously reported phenotypes. To better define the molecular mechanisms leading to this novel clinical presentation, we used CRISPR/Cas techniques to introduce the corresponding mutations in the mouse Foxn1 sequence. We will present data on the phenotypes of these mice, using intercrosses between individual mutant mice. Comparative transcriptome analyses of fetal thymii from these mice will reveal how the Foxn1 mutations impacts thymic epithelial gene expression and function compared to normal Foxn1. Our findings may lead to better understanding of the role of Foxn1 epithelial cell development and function in both the thymus and skin.

also postulated that antibiotics profoundly affect the symbiotic relationship between gut flora and the immune system, ultimately modifying the nature and intensity of the human immune response. The combination of these 2 factors may lead to the immunologic changes that lead to asthma.