A5066300435- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Hematopoietic Stem Cell Transplantation
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Reproductive Physiology in Livestock
- CAR-T cell therapy research
- Retinoids in leukemia and cellular processes
- Genetic and phenotypic traits in livestock
- Transplantation: Methods and Outcomes
- Phytoestrogen effects and research
- Immune cells in cancer
- Ruminant Nutrition and Digestive Physiology
- Histone Deacetylase Inhibitors Research
- Clinical Nutrition and Gastroenterology
- Diabetes and associated disorders
- Cancer Cells and Metastasis
- Acute Myeloid Leukemia Research
- Renal Transplantation Outcomes and Treatments
- Mast cells and histamine
- Chemokine receptors and signaling
- Synthesis of Tetrazole Derivatives
- Autoimmune Bullous Skin Diseases
- Cystic Fibrosis Research Advances
- Liver physiology and pathology
University of Minnesota
2015-2024
University of Alberta
2009-2024
University of Minnesota Medical Center
2016-2023
Masonic Cancer Center
2021
Food & Nutrition
2008
Technology Centre Prague
2008
Regulatory T cells (Tregs) subdue immune responses. Central to Treg activation are changes in lipid metabolism that support their survival and function. Fatty acid binding proteins (FABPs) a family of chaperones required facilitate uptake intracellular trafficking. One member, FABP5, is expressed cells, but its function remains unclear. We show Tregs, genetic or pharmacologic inhibition FABP5 causes mitochondrial underscored by decreased OXPHOS, impaired metabolism, loss cristae structure....
Corticosteroid treatment (CST) failure is associated with poor outcomes for patients gastrointestinal graft-versus-host disease (GI GVHD). CST intended to target the immune system, but glucocorticoid receptor widely expressed, including within intestines, where its effects are poorly understood. Here, we report that corticosteroids directly intestinal epithelium, potentially worsening immune-mediated GI damage. Corticosteroids administered mice in vivo and organoid cultures ex reduced...
Programmed death ligand-1 (PD-L1) interaction with PD-1 induces T cell exhaustion and is a therapeutic target to enhance immune responses against cancer chronic infections. In murine bone marrow transplant models, PD-L1 expression on host tissues reduces the incidence of graft-versus-host disease (GVHD). also expressed cells; however, it unclear whether this population influences function. Here, we examined effects modulation function in GVHD. patients severe GVHD, was increased donor cells....
The clinical success of chimeric antigen receptor (CAR) T cell therapy for CD19+ B malignancies can be limited by acute toxicities and immunoglobulin replacement needs due to aplasia from persistent CAR cells. Life-threatening complications include cytokine release syndrome neurologic adverse events, the exact etiologies which are unclear. To elucidate underlying toxicity mechanisms test potentially safer cells, we developed a mouse model in human CD19 (hCD19)-specific cells were adoptively...
Lymphopenia driven T cell activation is associated with autoimmunity. That lymphopenia does not always lead to autoimmunity suggests that control mechanisms may exist. We assessed the importance of co-inhibitory receptor programmed death-1 (PD-1) in lymphopenia-driven newly generated cells vs. established peripheral and thymic selection. PD-1 was required for negative selection thymus or maintenance self tolerance following transfer PD-1⁻/⁻ a lymphopenic host. In contrast, essential systemic...
Regulatory T cells (Tregs) are critical for maintaining immune homeostasis. However, current Treg immunotherapies do not optimally treat inflammatory diseases in patients. Understanding the cellular processes that control function may allow augmentation of therapeutic efficacy. In contrast to activated conventional cells, which protein kinase C-θ (PKC-θ) localizes contact point between and antigen-presenting human mouse Tregs, PKC-θ opposite end cell distal pole complex (DPC). Here, using a...
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) efficacy is complicated by graft-versus-host disease (GVHD), a leading cause of morbidity and mortality. Regulatory T cells (Tregs) have shown in preventing GVHD. However, high Treg doses are often required, necessitating substantial ex vivo or expansion that may diminish suppressor function. To enhance function, murine Tregs were transduced to express an anti-human CD19 chimeric antigen receptor (hCAR19) infused into lethally...
The expression of the coinhibitor PD-1 on T cells is important for establishment immune homeostasis. We previously found that particularly critical control self-tolerance during lymphopenia-induced proliferation recent thymic emigrants (RTEs). Previous studies suggested modulates generation Treg cells, peripherally induced (pTreg) and controls Th17 cells. However, these conclusions were derived indirectly from ligand PD-L1, not itself. Herein we directly tested whether T-cell was needed cell...
Abstract Targeting coinhibitory T cell receptors using monoclonal antibodies attenuates autoimmune diabetes by altering lymphocyte number and function. The novel receptor BTLA may have a regulatory role in maintaining peripheral tolerance; however, its is unknown. In this study, we show that anti-BTLA mAb 6F7 selectively depleted pathogenic B CD4+ TH cells; enhanced the proportion of cells with forkhead box p3+ PD-1+CD4+ phenotype; increased production potentially protective (IL-10)...
Nearly forty years ago the concept was proposed that lymphocytes are negatively regulated by what now called co-inhibitory signals. Nevertheless, it is only more recent identification of numerous co-inhibitors and their critical functions has brought co-inhibition to forefront immunologic research. Although signals have been considered directly regulate conventional T cells, data indicated a convergence between other major negative control mechanism in periphery mediated regulatory cells....
Lymphopenia can result from various factors including viral infections, clinical interventions, or as a normal property of the fetal/neonatal period. T cells in lymphopenic environment undergo lymphopenia-induced proliferation (LIP) to fill available "niche" defined by peptide-MHC (pMHC) and homeostatic cytokine resources. We recently reported systemic autoimmunity following reconstitution lymphoid compartment Rag1-/- mice with PD-1-/- hematopoietic stem transfer thymocytes, but not...
Damage to the gastrointestinal tract following allogeneic hematopoietic stem cell transplantation is a significant contributor severity and perpetuation of graft-versus-host disease. In preclinical models clinical trials, we showed that infusing high numbers regulatory T cells reduces disease incidence. Despite no change in vitro suppressive function, transfer ex vivo expanded transduced overexpress G protein-coupled receptor 15 or C-C motif chemokine 9, specific homing receptors for colon...
The immune system of female H-2(b) (C57BL/6) mice is a strong responder against the male minor-H antigen. However rejection or acceptance such weakly mismatched grafts depends on type tissue transplanted. mechanism responsible for spontaneous graft acceptance, and its relationship to natural mechanisms tolerance self antigens unknown. Co-inhibitory molecules negatively regulate responses, are important tolerance. We examined whether co-inhibitory play critical role in "spontaneous" allograft...
Abstract An ongoing dilemma faced during an immune response is generating effective, often proinflammatory to eliminate pathogens and/or infected cells while also minimizing collateral damage adjacent noninfected tissues. The factors limiting bystander cell injury Ag-specific in vivo are largely unknown. In this study, using model of islet transplants TCR transgenic mice, we show that both CD4 and CD8 T do have the capacity inflict tissue greatly enhanced sensitized hosts. cell–mediated...
Abstract Several coinhibitory receptors are upregulated upon activation, whereas a small number of expressed constitutively by naive T cells. The relationship between coinhibitors is unknown. We found an inverse two coinhibitors, CD5 and BTLA; BTLA expression was low in the thymus high periphery, corresponding respectively with expression. Germline or induced deletion Btla somatic cells demonstrated causal levels central peripheral lymphoid tissues. effect on thymic CD4 due to signaling,...