A5066311808- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Mast cells and histamine
- Neuroinflammation and Neurodegeneration Mechanisms
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Cytomegalovirus and herpesvirus research
- Allergic Rhinitis and Sensitization
- Urticaria and Related Conditions
- interferon and immune responses
- Celiac Disease Research and Management
- Immune cells in cancer
- RNA Research and Splicing
- Receptor Mechanisms and Signaling
- Tryptophan and brain disorders
- Chemical Synthesis and Analysis
- Influenza Virus Research Studies
- Immune Response and Inflammation
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- NF-κB Signaling Pathways
- Multiple Sclerosis Research Studies
- Psoriasis: Treatment and Pathogenesis
- Dermatology and Skin Diseases
Washington University in St. Louis
2020-2024
Hope Center for Neurological Disorders
2023-2024
Stanford University
2018-2022
Stratford University
2018
University of Vermont Medical Center
2015
University of Vermont
2008-2015
In this work, we find that CD8
Highly effective vaccines elicit specific, robust, and durable adaptive immune responses. To advance informed vaccine design, it is critical that we understand the cellular dynamics underlying responses to different antigen formats. Here, sought how antigen-specific B T cells were activated participated in within mucosal site. Using a human tonsil organoid model, tracked differentiation kinetics of response influenza virus modalities. Each format elicited distinct cell responses, including...
Recent single-cell RNA sequencing studies have revealed distinct microglial states in development and disease. These include proliferative-region-associated microglia (PAMs) developing white matter disease-associated (DAMs) prevalent various neurodegenerative conditions. PAMs DAMs share a similar core gene signature. However, the extent of dynamism plasticity these states, as well their functional significance, remains elusive, partly due to lack specific tools. Here, we generated an...
Understanding the DNA elements that constitute and control regulatory genome is critical for appropriate therapeutic management of complex diseases. Here, using chromosome Y (ChrY) consomic mouse strains on C57BL/6J (B6) background, we show susceptibility to two diverse animal models autoimmune disease, experimental allergic encephalomyelitis (EAE) myocarditis, correlates with natural variation in copy number Sly Rbmy multicopy ChrY genes. On B6 possesses gene properties impact genome-wide...
Germline gain-of-function (GOF) variants in STAT3 cause an inborn error of immunity associated with early-onset poly-autoimmunity and immune dysregulation. To study tissue-specific dysregulation, we used a mouse model carrying missense variant (p.G421R) that causes human disease. We observed spontaneous imiquimod (IMQ)-induced skin inflammation cell-intrinsic local Th17 responses GOF mice. CD4+ T cells were sufficient to drive showed increased Il22 expression expanded clones. Certain aspects...
Abstract Histamine is a biogenic amine that mediates multiple physiological processes, including immunomodulatory effects in allergic and inflammatory reactions, also plays key regulatory role experimental encephalomyelitis, the autoimmune model of sclerosis. The pleiotropic histamine are mediated by four G protein-coupled receptors, as follows: Hrh1/H1R, Hrh2/H2R, Hrh3/H3R, Hrh4/H4R. H4R expression primarily restricted to hematopoietic cells, its demyelinating disease CNS has not been...
Abstract Coxsackievirus B3 (CVB3) contributes to the development of myocarditis, an inflammatory heart disease that predominates in males, and infection is a cause unexpected death young individuals. Although gonadal hormones contribute significantly sex differences, chromosomes may also influence disease. Increasing evidence indicates Chromosome Y (ChrY) genetic variants can impact biological functions unrelated sexual differentiation. Using C57BL/6J (B6)-ChrY consomic mice, we show...
We investigated the genetic cause of disease in five affected individuals from two unrelated families with an autosomal dominant pattern invasive Streptococcus pneumoniae infection associated a clinical phenotype specific antibody deficiency. In Family A, male siblings presented at <5 years sepsis due to S. pneumoniae. The father had history meningitis and recurrent pneumonias, female sibling less severe infections. B, during infancy no family immunodeficiency. All patients...
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system in which histamine (HA) and its receptors have been implicated pathogenesis. HA exerts effects through four different G protein-coupled designated H(1)-H(4). We previously examined traditional single receptor (HR) knockouts (KOs) experimental allergic encephalomyelitis (EAE), autoimmune model MS. Our results revealed that H(1) R H(2) are propathogenic, while H(3) H(4) antipathogenic. This...
The major histocompatibility complex (MHC) is the primary genetic contributor to multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), but additional interacting loci are required for susceptibility. identity of most these non-MHC genes unknown. In this report, we identify within evolutionarily conserved pathways leading MS EAE.To binary quantitative trait (BTL/QTL) important in pathogenesis EAE, generated phenotype-selected congenic mice using EAE-resistant B10.S...
Abstract Histamine (HA) is a key regulator of experimental allergic encephalomyelitis (EAE), the autoimmune model multiple sclerosis. HA exerts its effects through four known G-protein–coupled receptors: H1, H2, H3, and H4 (histamine receptors; H1–4R). Using HR-deficient mice, our laboratory has demonstrated that H1R, H2R, H3R, H4R play important roles in EAE pathogenesis, by regulating encephalitogenic T cell responses, cytokine production APCs, blood–brain barrier permeability, regulatory...
Multiple sclerosis (MS) is a debilitating chronic inflammatory disease of the nervous system that affects approximately 2.3 million individuals worldwide, with higher prevalence in females, and strong genetic component. While over 200 MS susceptibility loci have been identified GWAS, underlying mechanisms whereby they contribute to remains ill-defined. Forward genetics approaches using conventional laboratory mouse strains are useful identifying functionally dissecting genes controlling...
Abstract Previous reports show a small subset of CD8+ T cells expressing Ly49 proteins in mice can suppress autoimmunity model demyelinating disease. Here we find markedly increased frequency inhibitory Killer cell Immunoglobulin like Receptors (KIR), the human equivalent family, blood and inflamed tissues various autoimmune diseases. Increased KIR+ gut also correlate with disease activity Celiac (CeD) patients. Moreover, efficiently eliminate pathogenic gliadin-specific CD4+ from CeD...
98% of T cells reside in tissues, yet nearly all human cell analyses are performed from peripheral blood. We single-cell sequenced 5.7 million ten donors' autologous blood and tonsils sought to answer key questions about receptor biology previously unanswerable by smaller-scale experiments. identified distinct clonal expansions distributions compared tonsils, with surprisingly low (1-7%) sharing. These few shared clones exhibited divergent phenotypes across bodily sites. Analysis...
Abstract Structural polymorphisms (L263P, M313V, and S331P) in the third intracellular loop of murine histamine receptor H1 (H1R) are candidates for Bphs, a shared autoimmune disease locus experimental allergic encephalomyelitis orchitis. The P-V-P haplotype is associated with increased susceptibility (H1RS) whereas L-M-S less severe (H1RR). In this study, we show that selective re-expression H1RS allele T cells fully complements production disease-associated cytokines while H1RR does not....
Abstract CMV infection is a significant complication after solid organ transplantation. We used single cell TCR αβ sequencing to determine how memory inflation impacts clonality and diversity of the CMV-responsive CD8 CD4 T repertoire in first year transplantation human subjects. observed but no changes clonal diversity, indicating homeostatic stability clones. In contrast, was diverse stable over time, with evidence expansion. identified shared CDR3 motifs among patients public CMV-specific...