A5007290314- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Ion Channels and Receptors
- Immunotherapy and Immune Responses
- MicroRNA in disease regulation
- Phytochemicals and Antioxidant Activities
- Neurobiology and Insect Physiology Research
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Neuroscience and Neuropharmacology Research
- Diabetes and associated disorders
- Hematopoietic Stem Cell Transplantation
- Ion channel regulation and function
- Genomic variations and chromosomal abnormalities
- Immune Response and Inflammation
- IL-33, ST2, and ILC Pathways
- Systemic Lupus Erythematosus Research
- RNA regulation and disease
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
Pennsylvania State University
2019-2025
Thomas Jefferson University
2025
Walsh University
2023
Hershey (United States)
2022
Germinal centers (GCs), sites of antibody affinity maturation, are organized into dark (DZ) and light (LZ) zones. Here, we show a B cell-intrinsic role for signal transducer activator transcription 3 (STAT3) in GC DZ LZ organization. Altered zonal organization STAT3-deficient GCs dampens development long-lived plasma cells (LL-PCs) but increases memory (MBCs). In an abundant antigenic environment, achieved here by prime-boost immunization, STAT3 is not required initiation, maintenance, or...
The essential role of store-operated Ca 2+ entry (SOCE) through release-activated (CRAC) channels in T cells is well established. In contrast, the contribution individual Orai isoforms to SOCE and their downstream signaling functions B are poorly understood. Here, we demonstrate changes expression response cell activation. We show that both Orai3 Orai1 mediate native CRAC cells. combined loss Orai3, but not alone, impairs SOCE, proliferation survival, nuclear factor activated (NFAT)...
Abstract How IRF7 promotes autoimmune B cell responses and systemic autoimmunity is unclear. Analysis of spontaneous SLE-prone mice deficient in uncovered the role regulating germinal center (GC), plasma (PC) autoantibody disease. IRF7, however, was dispensable for foreign antigen driven GC, PC antibody responses. Competitive bone marrow (BM) chimeras highlighted importance hematopoietic cells GC differentiation. Single-cell-RNAseq indicated mediated differentiation through fates....
How IRF7 promotes autoimmune B cell responses and systemic autoimmunity is unclear. Analysis of spontaneous SLE-prone mice deficient in uncovered the role regulating germinal center (GC), plasma (PC), autoantibody disease. IRF7, however, was dispensable for foreign antigen–driven GC, PC, antibody responses. Competitive bone marrow (BM) chimeras highlighted importance hematopoietic cells GC PC differentiation. Single-cell RNAseq indicated IRF7-mediated differentiation through fates....
The SOX transcription factor family is pivotal in controlling aspects of development. To identify genotype-phenotype relationships proteins, we performed a non-biased study using 1890 open-reading frame and 6667 amino acid sequences combination with structural dynamics to interpret 3999 gnomAD, 485 ClinVar, 1174 Geno2MP, 4313 COSMIC human variants. We identified, within the HMG (High Mobility Group)- box, twenty-seven acids changes multiple proteins annotated clinical pathologies. These...
Abstract MicroRNAs (miRNAs) are involved in healthy B cell responses and the loss of tolerance systemic lupus erythematosus (SLE), although role many miRNAs remains poorly understood. Dampening miR-21 activity was previously shown to reduce splenomegaly blood urea nitrogen levels SLE-prone mice, but detailed cellular mechanism action unexplored. In this study, using TLR7 agonist, imiquimod-induced SLE model, we observed that Sle1b mice prevented formation plasma cells autoantibody-producing...
Genome-wide association studies identified variants in the transcription factor STAT4 gene and several other genes signaling pathway, such as IL12A, IL12B, JAK2, TYK2, which are associated with an increased risk of developing systemic lupus erythematosus (SLE) autoimmune diseases. Consistent genome-wide data, was shown to play important role responses autoimmunity development SLE mouse models. Despite for mice humans, little is known whether how may regulate extrafollicular Ab-forming cell...
Abstract Germinal centers (GCs) are essential for the production of somatically hypermutated, class-switched Abs that protective against infection, but they also form in absence purposeful immunization or and termed spontaneous GCs (Spt-GCs). Although Spt-GCs can arise nonautoimmune-prone mice, aberrant regulation autoimmune-prone mice is strongly associated with development autoimmune diseases like systemic lupus erythematosus. The formation crucially driven by TLR7-mediated RNA sensing....
Abstract The essential role of store-operated Ca 2+ entry (SOCE) through release-activated (CRAC) channels in T cells is well established. In contrast, the contribution individual Orai isoforms to SOCE and their downstream signaling functions B are poorly understood. Here, we demonstrate changes expression response cell activation. We show that Orai3 Orai1 components native CRAC critical for primary proliferation survival. combined loss strongly impairs SOCE, nuclear factor activated (NFAT)...
Abstract Germinal centers (GCs), sites of antibody affinity maturation, are organized into dark (DZ) and light (LZ) zones. Here, we uncovered a B cell intrinsic role for STAT3 in GC DZ LZ organization. Altered zonal organization STAT3-deficient GCs dampened output long-lived plasma cells (LL-PCs) but increased memory (MBCs). Tfh-GC interaction drive tyrosine 705 serine 727 phosphorylation cells, facilitating their recycling the DZ. An inducible system confirmed is not involved initiating or...
Abstract MicroRNAs (miRNAs) are involved in healthy B cell responses and the loss of tolerance systemic lupus erythematosus (SLE), though role many miRNAs remains poorly understood. Dampening miR-21 activity was previously shown to reduce splenomegaly blood urea nitrogen levels SLE-prone mice, but detailed cellular mechanism action unexplored. Herein, using TLR7 agonist imiquimod-induced SLE model, we observed that Sle1b mice prevented formation plasma cells autoantibody forming (AFC),...
Abstract MicroRNA-21 (miR-21) is upregulated in SLE patients and promotes disease multiple autoimmune mouse models; however, mechanisms by which miR-21 promote autoimmunity are unknown. Here we show that TLR7 overexpressing SLE-prone B6.Sle1b Yaamice deficient (Sle1b YaamiR-21 −/−) resisted development through reduced germinal center (GC) B cell, T follicular helper plasma cell responses. Sle1b −/−mice had serum autoantibody titers numbers of autoantibody-producing antibody forming cells...
Abstract Germinal centers (GCs) are sites for antibody diversification, somatic hypermutation (SHM) and antigen specific B cell selection. GCs anatomically divided into two distinct areas known as dark zone (DZ) light (LZ) where SHM clonal selection occurs, respectively. Although previous studies have suggested a cell-intrinsic role of STAT3 in GC maintenance responses, how signaling cells may maintain is not clear. Using immunization infection models, we show that regulates the DZ,...