Translational Immunology Core

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...

Middle East respiratory syndrome coronavirus (MERS-CoV) remains a low-incidence but high-consequence zoonotic coronavirus threat. Since its identification in Saudi Arabia in 2012, more than 2600 laboratory-confirmed cases have been reported from 27 countries, most from the Arabian Peninsula; the reported case fatality ratio is high but probably overestimates infection fatality because mild and asymptomatic infections are under-detected. Dromedary camels across the Middle East, North Africa, East...

Influenza A and B viruses are considerable public health threats. Annual seasonal epidemics are driven by antigenic drift and cause an estimated 3-5 million severe cases and 290,000-650,000 deaths annually. The clinical presentation of seasonal influenza is typically an abrupt, uncomplicated acute respiratory illness with full recovery; however, it can lead to severe, life-threatening complications in individuals at high risk. Antigenic shift caused by reassortment of a seasonal influenza A...

Oncogene SETDB1, an H3K9 methyltransferase, drives tumorigenesis in various cancers. Using endometrial cancer (EC) as a model, we discovered SETDB1's dual mechanisms in driving EC tumorigenesis and mediating immune evasion. SETDB1 knockout (SETDB1^(-/-)) tumor-bearing mice exhibited prolonged survival up to 100 days. Transcriptomic profiling of SETDB1^(-/-) EC cells revealed decreased oncogene expression and increased tumor suppressor gene expression, which indicates that SETDB1 intrinsically...

Chorioamnionitis is a common cause of perinatal inflammation and is associated with adverse neonatal and long-term outcomes. Although male infants experience higher rates and greater severity of many inflammation-related morbidities, the contribution of fetal sex to chorioamnionitis-related outcomes remains understudied. This review synthesizes evidence from human studies and animal models to evaluate how sexually dimorphic placental biology and fetal immune responses shape offspring...