Translational Immunology Core

CONCLUSION: Allergen challenge promotes diverse pro-inflammatory transcriptional responses in the airways, and MCs, basophils, and AECs play distinct but critical roles in coordinating this response. However, airway responses to allergen may vary considerably based on the baseline airway inflammatory endotype.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system in which environmental factors play an important role in shaping disease risk, activity, and progression. Over the past decade, human and experimental studies have consistently shown alterations in the gut microbiome across the phenotypic spectrum of MS and have linked these changes to immune dysregulation, barrier dysfunction, neuroinflammation, and demyelination. Additionally, emerging evidence indicates...

CONCLUSIONS: Controllable SB mutagenesis using DiSBey mice provides a novel platform for functional screening of genes that improve T-cell phenotypes important for their use as therapies. Our findings highlight a dose-dependent role of BACH2 in enhancing the function of engineered T cells under conditions of chronic antigenic stimulation.

CONCLUSIONS: This study redefines IL-17A's role in immune regulation, emphasizing its ability to directly influence gut microbiota composition and the abundance of Treg-promoting bacteria. Thus, gut microbiota-targeted therapies, particularly those promoting Treg-inducing bacteria like Prevotella species, hold promise for treating autoimmune diseases by modulating host immune responses. Video Abstract.

In meiosis, homologous recombination (HR) facilitates the halving of genomic content in diploid parents to produce haploid gametes, while also reshuffling genetic material. However, studies in yeast and mammals have suggested that HR during meiosis also makes the process mutagenic, and it has been proposed that the single-strand (ss) DNA formed by HR of programmed double-strand breaks (DSBs) contributes to the observed mutagenesis. To determine the full mutagenic potential of ssDNA formed during...

CONCLUSIONS: MMP9 genotype affects structural and functional outcomes in patients with nvAMD. Along with the observed systemic immune dysregulation, these findings support the role of a MMP9-dendritic-T-cell axis in nvAMD immunopathogenesis and highlight this as a potential therapeutic target.

Glycerol monolaurate (GML) is a fatty acid monoester of glycerol that is approved by the FDA as a food additive and component of cosmetics. We previously showed that 50,000 µg/mL of GML solubilized in the non-aqueous K-Y Warming Gel is broadly antibacterial, including S. aureus and various streptococcal species, and selectively increases beneficial lactobacilli. GML is also anti-inflammatory, reducing harmful inflammation. In the current study, we examined GML and longer or shorter fatty acid...

CONCLUSION: HLA mismatch is a stronger predictor of graft outcomes than KDPI in pediatric kidney transplantation. The limited number of high-KDPI donors in pediatric recipients may explain the lack of significant association with KDPI. These findings support efforts to minimize HLA mismatches in pediatric allocation strategies.

Premature termination codons (PTCs) are a major class of pathogenic variants that underlie rare inherited disorders, including forms of childhood blindness. Therapeutic suppression of these "nonsense mutations" offers a gene- and position-agnostic strategy to restore protein function. Our previous work established that the W53X PTC in the KCNJ13 gene causes Leber congenital amaurosis type 16 (LCA16) by disrupting the inwardly rectifying potassium channel Kir7.1, leading to retinal pigment...

CONCLUSION: Targeting LSD1 enhances the efficacy of anti-CD47 therapy by overcoming immune evasion, offering a promising strategy to improve immunotherapy outcomes in TNBC.