Translational Immunology Core

The Virtual Eye initiative described here seeks to build a versatile and integrative in silico platform, 'The Virtual Eye' that can capture and simulate the biology, physiology and function of the human eye, from molecular interactions to organ-level behaviour, in both healthy and diseased states. This effort has the potential to substantially deepen our understanding of the visual process, clarify the mechanistic basis of ocular diseases across multiple spatial and temporal scales, and support...

Small regulatory RNAs (sRNAs) are key drivers of bacterial adaptation to environmental fluctuations, including iron and manganese restriction imposed by the host. This study explored the repertoire of sRNAs produced by the human pathogen Staphylococcus aureus in response to metal limitation. Two sRNAs were identified, S1077 and ZinS, that were regulated by zinc (Zn) availability. Further investigations revealed that, similar to the cnt operon from which it derives, S1077 synthesis is controlled...

BACKGROUND: Asthma is a heterogeneous chronic disease, disproportionately affecting racial and ethnic minorities, with persistence and severity influenced by both environmental and genetic factors. The IL-4RαR576 variant occurs more commonly in racially minoritized, and the genotype, independent of race, is associated with severe, exacerbation-prone asthma. IDEA (Investigating Dupilumab's Effect in Asthma by genotype) NCT02570984 is a multicenter, randomized, placebo-controlled trial designed to...

The increasing demand for nuclear power and radiotherapy has expanded potential avenues for human exposure to whole-body irradiation (WBI), underscoring the need to understand its impact on immune cells. While prior studies have explored radiation-induced disruptions in immune homeostasis, the direct effect of WBI on pre-existing memory CD4 T cells remains elusive. Using T cell receptor transgenic CD4 T cell chimeric mice infected with lymphocytic choriomeningitis virus-Armstrong, we demonstrate...

BACKGROUND: Second-hand smoke (SHS) exposure remains a major source of morbidity and mortality among non-smokers. This study presents the first dedicated Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) publication to systematically quantify SHS prevalence and evaluate its effect as a global risk factor across a broader range of outcomes.

Obsessive-compulsive disorder (OCD) and chronic tic disorders (CTDs) are highly heritable. Rare mutations confer large risks for OCD and CTDs but only four high-confidence (hc) genes have been identified. Here we analyzed whole-exome sequencing data from 3,964 individuals with OCD, CTDs or both, including 2,418 trios. We found an excess in cases of de novo and rare protein-damaging mutations and identified 36 hc genes (false discovery rate < 0.1), including four previously identified hc genes...

INTRODUCTION: Borrelia burgdorferi (Bb) infection can persist in protected sites like articular joints, presenting as migratory oligoarthritis characteristic of Lyme Arthritis (LA). LA is characterized by intermittent synovitis and joint swelling, but why acute infection is relapsing-remitting and not persistent remains unknown. We hypothesize that the immune response is unique to the joint space, particularly the response of Resident Synovial Macrophages (RSMs), and may be important in...

Allergic asthma results from an uncontrolled type 2 immune response to inhaled allergens. Here, we investigate the function of CD97/ADGRE5, expressed in mouse and human immune and lung epithelial cells, in this disease. Female Cd97^(-/-) mice exhibit an exacerbated asthmatic phenotype across multiple models, primarily due to CD97 loss on immune cells. A single CD97 antibody treatment before allergen sensitization worsens allergic responses, highlighting a role for CD97 in early immune...

Polymorphic toxins mediate interbacterial antagonism among competitors in the gut microbiome. Nuclease effectors, distantly related to the type VI-secreted Bacteroidales Tde, are enriched in human gut Bacillota. Tde mediates antagonism among Bacillota, and expression of the cognate immunity, Tdi, in recipients is protective. Crystal structures of Tde/Tdi complexes from two Bacillus spp. and Enterococcus quebecensis highlight a conserved mechanism of immunity. Tdi engages Tde with high-affinity,...

Progesterone exerts important immunomodulatory functions, yet the immune effects of structurally diverse synthetic progestins remain incompletely defined. Given their variable receptor-binding profiles and links to altered inflammatory outcomes, we examined how commonly used progestins regulate immune signaling in primary human cells. Peripheral blood mononuclear cells from healthy female donors were exposed to physiologically relevant concentrations of natural progesterone (P4) and...