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Articles 1 - 30 of 47
Full-Text Articles in Medicine and Health Sciences
Identification Of Multi-Tissue Protein Quantitative Trait Loci And Causal Inference Of Protein Effects In Neurological And Other Complex Human Diseases Via Mendelian Randomization, Chengran Yang
Arts & Sciences Electronic Theses and Dissertations
Alzheimer disease (AD) is the most common neurodegenerative disease, affecting 6.2 million people mostly aged 65 years or older in the United States as of early 2021. AD has been widely studied and characterized worldwide, but there is still no effective treatment or cure. Even the latest FDA-approved treatment, Aducanumab, cannot stop decline or improve cognition. To develop a truly effective treatments, researchers keep discovering genetic and molecular mechanisms underlying the disease. Protein biomarkers are keys to bridge the mechanisms to disease. Here, I first used a high-throughput proteomic dataset from three tissues (CSF, plasma, and brain) with array-based genotype …
On Arousal And The Internal Regulation Of Brain Function: Theory And Evidence Across Modalities And Species, Ryan Raut
Arts & Sciences Electronic Theses and Dissertations
The brain is an organ. It is subject to the same physiological regulatory processes that engage the rest of the body’s organs, sculpted over hundreds of millions of years to sustain life so effectively. The central message of this thesis is that the holistic functioning of the brain, rather than operating at some level above or independent from these systemic regulatory processes, is deeply related to them. In short, as our limited attention spans might suggest: brain function is internally regulated. I propose that this internal regulation is a primary function of intrinsic brain activity. Chapter 2 provides a theoretical …
Slo2.1 Channels: A New Molecular Mechanism To Regulate Uterine Excitability, Juan Jose Ferreira
Slo2.1 Channels: A New Molecular Mechanism To Regulate Uterine Excitability, Juan Jose Ferreira
Arts & Sciences Electronic Theses and Dissertations
At the end of pregnancy, the uterus transitions from a non-contractile state to a highly contractile state. Two processes primarily drive this transition. First, from the 28th week of pregnancy until labor, the resting membrane potential of uterine (myometrial) smooth muscle cells (MSMCs) gradually becomes more positive (depolarizes) (Parkington et al. 1999). Second, at the end of pregnancy, MSMCs express more oxytocin receptors and become more sensitive to oxytocin (Kimura et al. 1996). However, the detailed mechanisms by which these processes occur have not been determined. My central hypothesis was that the Na+-activated K+ channel SLO2.1 plays a key role …
The Role Of Neuronal Atp-Sensitive Potassium Channels In Learning And Memory, Shaul Vladimir Yahil
The Role Of Neuronal Atp-Sensitive Potassium Channels In Learning And Memory, Shaul Vladimir Yahil
Arts & Sciences Electronic Theses and Dissertations
ATP-sensitive potassium (KATP) channels link cellular metabolism and membrane excitability in many tissues, including brain and pancreas. Gain-of-function (GOF) mutations to KATP channels cause neonatal diabetes, with some patients exhibiting developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome. Diabetic symptoms have been attributed to loss of membrane excitability and insulin secretion in pancreatic β-cells, though the origin of neurological deficits and the effects of neuronal KATP-GOF mutations more generally remain elusive. In this dissertation, I will present evidence that mice expressing KATP-GOF mutations pan-neuronally (nKATP-GOF) demonstrated sensorimotor and cognitive deficits, whereas hippocampus-specific hKATP-GOF mice exhibited predominantly learning and memory deficits. …
Genetic Risk Factors For Neurodevelopmental Disorders: Insights From Hipsc-Cerebral Organoids, Michelle L. Wegscheid
Genetic Risk Factors For Neurodevelopmental Disorders: Insights From Hipsc-Cerebral Organoids, Michelle L. Wegscheid
Arts & Sciences Electronic Theses and Dissertations
Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder (NDD) characterized by remarkable phenotypic variability, where affected children manifest a spectrum of central nervous system (CNS) abnormalities, including brain tumors, impairments in attention, behavior, learning disabilities, and an increased incidence of autism spectrum disorder (ASD). A significant barrier to the implementation of precision medicine strategies for children with NF1 is a lack of prognostic risk factors to guide clinical management. However, emerging population-based genotype-phenotype association studies have suggested that the germline NF1 gene mutation may represent one clinically actionable risk factor for NF1-associated neurodevelopmental abnormalities. As a critical step in …
Causal Function And Bias Correlation Of The Orbitofrontal Cortex In Economic Choices, Shi Weikang
Causal Function And Bias Correlation Of The Orbitofrontal Cortex In Economic Choices, Shi Weikang
Arts & Sciences Electronic Theses and Dissertations
Economic choices entail two mental processes, value calculation and value comparison (Niehans, 1990). Studies in the last twenty years have shown that neurons in the orbitofrontal cortex (OFC) could support both processes. Namely, in the studies in which monkeys chose between two juice options with various amounts, three functional cell groups had been found in the OFC: offer value cells encode the value of individual juices, chosen juice cells encode the choice in a binary way and chosen value cells encode the value of the chosen juice (Padoa-Schioppa and Assad, 2006). These results suggest a decision circuit within OFC with …
Influence Of Focal Activity On Macroscale Brain Dynamics In Health And Disease, Zachary Pollack Rosenthal
Influence Of Focal Activity On Macroscale Brain Dynamics In Health And Disease, Zachary Pollack Rosenthal
Arts & Sciences Electronic Theses and Dissertations
Macroscopic recordings of brain activity (e.g. fMRI, EEG) are a sensitive biomarker of the neural networks supporting neurocognitive function. However, it remains largely unclear what mechanisms mediate changes in macroscale networks after focal brain injuries like stroke, seizure, and TBI. Recently, optical neuroimaging in animal models has emerged as a powerful tool to begin addressing these questions. Using widefield imaging of cortical calcium dynamics in mice, this dissertation investigates the mechanisms by which focal disruptions in activity alter brain-wide functional dynamics. In two chapters, I demonstrate 1) that focal sensory stimulation elicits state-dependent, global slow waves propagating from primary somatosensory …
Defining The Epigenetic And Transcriptional Regulatory Mechanisms By Which Hrsv Ns1 Alters Host Transcriptional Response, Nina Rose Beri
Defining The Epigenetic And Transcriptional Regulatory Mechanisms By Which Hrsv Ns1 Alters Host Transcriptional Response, Nina Rose Beri
Arts & Sciences Electronic Theses and Dissertations
No abstract provided.
Influence Of Aging And Cerebrovascular Disease On Neuroimaging Measures Of Alzheimer Disease, Lauren Nicole Koenig
Influence Of Aging And Cerebrovascular Disease On Neuroimaging Measures Of Alzheimer Disease, Lauren Nicole Koenig
Arts & Sciences Electronic Theses and Dissertations
The overall goal of this dissertation is to gain a better understanding of how Alzheimer disease relates to normal aging and cerebrovascular disease to impact neuroimaging measures in a clinically meaningful way. Both aging and cerebrovascular disease are known to influence measures of Alzheimer disease, making it difficult to separate what changes are attributable specifically to Alzheimer disease. We hypothesize that a better understanding of these relationships will allow future studies to appropriately take these factors into account. In Chapters 2 and 3 we attempt to separate out the influences of normal aging and Alzheimer disease on measures of atrophy. …
The Potential Of Mental Health Policy Implementation: Methods And Applications, Meagan Renee Pilar
The Potential Of Mental Health Policy Implementation: Methods And Applications, Meagan Renee Pilar
Arts & Sciences Electronic Theses and Dissertations
Mental illness affects roughly 20% of the world in some capacity and can be debilitating. Though a large emphasis has historically been placed on individual-level interventions (e.g., therapy or medication), mental health policies present an opportunity to intervene on a large scale, with the potential to enhance impact and equity. This dissertation contributes to the mental health policy research literature in three main ways—(1) exploring factors affecting policymakers’ overall support of mental health policies; (2) assessing the use and quality of quantitative and qualitative methods within this field; and (3) exploring implementation determinants and outcomes, as well as strategies used …
Structural Analysis And Vaccine Efficacy Of Hla Mutants, Kelly Tomaszewski
Structural Analysis And Vaccine Efficacy Of Hla Mutants, Kelly Tomaszewski
Arts & Sciences Electronic Theses and Dissertations
Staphylococcus aureus is a commensal of the human skin and also a major human pathogen. Currently, there has been no successful vaccine despite many approaches over the last two decades. S. aureus α-hemolysin (Hla), a potent cytotoxin, plays an important role in the pathogenesis of S. aureus diseases, through the activation of its receptor, ADAM10. We utilized three distinct Hla mutants with differing structural and ADAM10 binding properties to examine for vaccine efficacy. Our studies have demonstrated immunization with each vaccine candidate antigens provided significant protection against S. aureus skin infection yet elicited distinguishable immune responses. We have also generated …
Movement Patterns During Functional Activities In People With Chronic Low Back Pain, Quenten Lowell Hooker
Movement Patterns During Functional Activities In People With Chronic Low Back Pain, Quenten Lowell Hooker
Arts & Sciences Electronic Theses and Dissertations
People with chronic LBP display an altered movement pattern where the lumbar spine moves more readily than other joints that can contribute to the activity. The pattern is of particular clinical relevance because across multiple studies the magnitude of altered pattern is associated with LBP and function. One session of motor skill training (MST) during functional activities can improve the altered pattern. However, of the few studies investigating MST for people with LBP, none have examined the short-term or long-term effects of MST on the altered pattern. Additionally, no study has systematically examined if person-specific characteristics moderate the altered pattern …
The Immunoregulation Of Autoimmune Diabetes, Hao Hu
The Immunoregulation Of Autoimmune Diabetes, Hao Hu
Arts & Sciences Electronic Theses and Dissertations
How autoimmune diseases are regulated is a long-term research topic in the autoimmunity field. We use autoimmune diabetes as a model to study this. Autoimmune diabetes is a T cell-dependent autoimmune syndrome. The functions of T cells are regulated during their development and activation. Developmentally, T cells will undergo a stringent thymic selection: a process that self-reactive T cells are tolerized to become thymic derived Tregs or can be deleted by apoptosis based on binding affinity and avidity between the TCRs and self-peptide:MHC complexes. After T cells mature, they can also be tolerized in the periphery in many other ways, …
Investigating The Role Of Bladder Epithelial Stem Cells In Bladder Mucosal Remodeling And Defense Against Infection, Seongmi Kim Russell
Investigating The Role Of Bladder Epithelial Stem Cells In Bladder Mucosal Remodeling And Defense Against Infection, Seongmi Kim Russell
Arts & Sciences Electronic Theses and Dissertations
Urinary tract infections (UTIs) can be highly recurrent, and the mechanism(s) governing recurrence susceptibility are mostly unknown. Here I demonstrate bladder epithelial (urothelial)-intrinsic trained immunity as part of a differential mucosal remodeling response to an initial UTI. I established urothelial stem cell (USC) lines from isogenic mice with different UTI histories (naïve, chronic, or self-resolving) and discovered 2880 differential genome-accessible regions, indicating differential epigenetic reprogramming dependent on infection history. Differentiation of USC lines in vitro resulted in polarized urothelial cultures that recapitulated distinct remodeling morphologies seen in vivo and exhibited altered gene expression, including genes involved in cell death pathways. …
Exploring Contextual Differences In Environment And Policy Strategies To Promote Physical Activity In Disadvantaged Communities, Natalicio Hector Serrano
Exploring Contextual Differences In Environment And Policy Strategies To Promote Physical Activity In Disadvantaged Communities, Natalicio Hector Serrano
Arts & Sciences Electronic Theses and Dissertations
The benefits of physical activity for health are far reaching, including the reduced risk of several chronic diseases. However, only about 24% of US adults meet recommended guidelines of physical activity, with traditionally disadvantaged populations such as rural residents and persons of color facing even lower rates. Ecological models of health behavior help to understand correlates of physical activity that impact population health, but may not be as useful in disadvantaged populations where the evidence base is either lacking or not as rigorous. Furthermore, measures and methods may be underdeveloped in disadvantaged populations and there is a lack of understanding …
Exploring Β-Cell Function And Heterogeneity In Obese Sm/J Mice, Mario Alejandro Miranda
Exploring Β-Cell Function And Heterogeneity In Obese Sm/J Mice, Mario Alejandro Miranda
Arts & Sciences Electronic Theses and Dissertations
Pancreatic β-cells perform glucose-stimulated insulin secretion, a process required to maintain systemic glucose homeostasis. Obesity promotes glycemic and inflammatory stress, causing β-cell death and dysfunction, resulting in diabetes. Efforts to improve β-cell function in obesity have been hampered by observations that β-cells are highly heterogeneous, varying in morphology, function, and gene expression. There is great need to understand the breadth of β-cell heterogeneity in health and obesity to improve diabetic therapies.High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we show that as they resolve hyperglycemia, obese SM/J …
Phenotyping And Preclinical Meta-Analysis Of Behavioral Outcomes From Complete Freund’S Adjuvant-Induced Inflammatory Pain In The Rodent Hind-Paw, Dominika J. Burek
Phenotyping And Preclinical Meta-Analysis Of Behavioral Outcomes From Complete Freund’S Adjuvant-Induced Inflammatory Pain In The Rodent Hind-Paw, Dominika J. Burek
Arts & Sciences Electronic Theses and Dissertations
Pain and opioid use disorder prevalence, diagnoses of mental health disorders, and rate of suicide have all skyrocketed over the last 30 years as a matrix of public health crises. Each reduces quality of life and installs risk of the others; together, they have burdened our country with nearly unmanageable healthcare challenges. Although the critical demand for novel and more effective therapeutics has been clear for decades, relatively little progress has been made to address pain and its comorbidities. Repeated clinical trial failures have called into question the preclinical evidence upon which they are based. Preclinical models of pain-induced negative …
Investigation Of Ifnγ-Induced Control Of Intracellular Pathogens, Michael Mcallaster
Investigation Of Ifnγ-Induced Control Of Intracellular Pathogens, Michael Mcallaster
Arts & Sciences Electronic Theses and Dissertations
Genes required for the lysosomal degradation pathway of autophagy play key roles in topologically distinct cellular processes with significant physiologic importance. One of the first-described of these ATG gene-dependent processes is the requirement for a subset of ATG genes in interferon-γ (IFNγ)-induced inhibition of norovirus and Toxoplasma gondii replication. In this dissertation we identified novel components that are required for or that negatively regulate this immune mechanism. Enzymes involved in the conjugation of UFM1 to target proteins including UFC1 and UBA5, negatively regulated IFNγ-induced inhibition of norovirus replication via effects of Ern1. We identified and confirmed that IFNγ-induced inhibition of …
Metabolic Control And Immune Barriers Of Hematopoietic Stem Cells, Hannah Pizzato
Metabolic Control And Immune Barriers Of Hematopoietic Stem Cells, Hannah Pizzato
Arts & Sciences Electronic Theses and Dissertations
Hematopoietic stem cells (HSCs) have the unique ability to self-renew for life, to differentiate into mature blood lineages, and to readily engraft upon intravenous transplantation. As such, they are the only types of stem cells in routine clinical use. Understanding HSCs and hematopoietic development can provide many lessons for other types of stem cells as they near clinical utility. Through bone marrow transplantation, it was discovered that cells exist with regenerative potential. This led to the search to purify these cells and to determine the function of other hematopoietic cells. By isolating and transplanting cells expressing different combinations of surface …
Exploring The Intrinsic And Extrinsic Factors That Regulate Breast Cancer Cell Dormancy, Qihao Ren
Exploring The Intrinsic And Extrinsic Factors That Regulate Breast Cancer Cell Dormancy, Qihao Ren
Arts & Sciences Electronic Theses and Dissertations
Breast cancer can recur in patients months to decades after initial diagnosis and treatment. There is mounting evidence that dormant breast disseminated tumor cells (DTCs) exist in distant organs, whose reactivation results in cancer recurrence. However, the mechanisms that control tumor cell dormancy remain poorly understood, making it difficult to predict which patients will recur and develop cancer recurrence. Unfortunately, the extreme rarity of dormant DTCs has been the major obstacle to their study. To overcome this challenge, we developed an efficient system to isolate and study rare dormant tumor cells from metastatic organs. Using this system and single cell …
Discovery Of Sex Differences In Response To P53 Loss And Gain-Of-Function In Glioblastoma, Nathan Cuyle Rockwell
Discovery Of Sex Differences In Response To P53 Loss And Gain-Of-Function In Glioblastoma, Nathan Cuyle Rockwell
Arts & Sciences Electronic Theses and Dissertations
The tumor suppressor TP53 (p53) is the most frequently mutated gene in cancer and among the most mutated genes in brain cancer. Functionally, p53 is a transcription factor that, when activated by an array of stress stimuli, regulates a complex transcriptional program that contributes to a variety of antiproliferative pathways. The loss of p53 function (LOF), either through mutation, deletion, or inhibition by alterations in the proteins that regulate p53, removes an essential barrier to the unfettered proliferation and genomic instability that drive transformation. Unlike most tumor suppressors, many p53 mutations are missense mutations that lead to stable expression of …
Regulation Of Host-Microbe Interactions In Autoimmunity And Antiviral Immunity By Cytosolic Nucleic Acid Sensing And Interferon Signaling, Derek Jerome Platt
Regulation Of Host-Microbe Interactions In Autoimmunity And Antiviral Immunity By Cytosolic Nucleic Acid Sensing And Interferon Signaling, Derek Jerome Platt
Arts & Sciences Electronic Theses and Dissertations
Cytosolic nucleic acid sensing and interferon (IFN) signaling are central to the host immune response to microbial pathogens. However, dysregulation of immunological pathways such as these can result in devastating autoimmune disease. In order to provide a robust immune response to pathogen without causing harm to self, the host immune system must engage in a delicate balancing act, interacting with microbes and determining whether they are commensal or pathogenic. The cGAS-STING pathway is a key regulator of host-microbe interactions by cytosolic nucleic sensing and IFN signaling. Loss of function in the cGAS-STING pathway leads to increased susceptibility to pathogenic threats, …
Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc
Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc
Arts & Sciences Electronic Theses and Dissertations
Rapid cell proliferation is a hallmark feature of adaptive immune cells lymphocytes. It is essential for the establishment of diverse antigen receptor repertoires and amplification of antigen-specific immune responses. While such proliferation is beneficial for host protection from infections and cancers, it inevitably elevates the risk of oncogenic transformation. In developing and germinal center B lymphocytes, the risk is further increased by endogenous, genomic insults due to antigen receptor rearrangements and somatic mutations, with which expression of the proto-oncogene c-MYC is closely associated. Nonetheless, frequencies of cancers originated from B lymphocytes are relatively low, suggesting that they are protected from …
Peripheral Nerve Macrophages And Their Implications In Neuroimmunity, Peter Leon Wang
Peripheral Nerve Macrophages And Their Implications In Neuroimmunity, Peter Leon Wang
Arts & Sciences Electronic Theses and Dissertations
Macrophages are innate immune cells that protect against pathogens and maintain tissue integrity. In vertebrates, macrophages reside in every tissue where they perform specific functions from early development through adulthood. While macrophages provide important functions across all tissues, a major focus in recent years has been the role of resident brain macrophages, known as microglia, in neurodegeneration. As microglia have been shown to affect brain development, homeostasis, and disease, they demonstrate how immune cells critically mediate neurological health and point to the broader significance of neuroimmune interactions, or the coordinated actions of the nervous and immune systems for maintaining tissue …
Role Of 4r Tau In Astrocyte-Mediated Neuronal Toxicity And The Progression Of Neurodegenerative Disease, Lubov Alexandra Ezerskiy
Role Of 4r Tau In Astrocyte-Mediated Neuronal Toxicity And The Progression Of Neurodegenerative Disease, Lubov Alexandra Ezerskiy
Arts & Sciences Electronic Theses and Dissertations
The microtubule-binding protein tau is associated with neurodegenerative diseases, including Alzheimer’s disease, progressive supranuclear palsy, and a subset of frontotemporal dementias. In these tauopathies, tau becomes hyperphosphorylated and forms intracellular neurofibrillary tau tangles, contributing to synaptic dysfunction, neuronal death, and severe astrogliosis. Tau can be classified as having a 3-repeat (3R) or 4-repeat (4R) structure, resulting from alternative splicing of exon 10 within the MAPT gene. While the higher deposition of 4R tau characterizes many primary tauopathies, the role of 4R tau in neurodegenerative disease pathogenesis remains unclear. To investigate the role of tau isoforms in disease, we created tau …
A Secondary Data Analysis Of The Prevalence Of Reported Dementia And Subjective Cognitive Decline Across U.S. National Surveys, Matthew C. Picchiello
A Secondary Data Analysis Of The Prevalence Of Reported Dementia And Subjective Cognitive Decline Across U.S. National Surveys, Matthew C. Picchiello
Arts & Sciences Electronic Theses and Dissertations
Within the United States, many large-scale, nationally representative studies exist with the goal of tracking and monitoring aspects of health. These studies are often used to establish the prevalence of dementia and subjective cognitive decline (SCD) in the population. The goal of the current study is to examine how different population-based studies probe respondents about conditions related to cognitive impairment, and to assess similarities and differences in point estimates. We reviewed eight studies and identified comparable items related to dementia and SCD. We calculated design-appropriate point prevalence estimates and compared weighted estimates across studies, finding a wide range and statistically …
Dissecting The Role And Regulation Of Transcription Factor Zeb2 In Hematopoiesis, Xiao Huang
Dissecting The Role And Regulation Of Transcription Factor Zeb2 In Hematopoiesis, Xiao Huang
Arts & Sciences Electronic Theses and Dissertations
A potent immune response requires crosstalk and collaboration between the innate and adaptive immune systems, both of which contain highly specialized immune lineages. All immune lineages arise during adult life are generated from the differentiation of hematopoietic stem cells (HSCs) in the process of hematopoiesis. Normal hematopoiesis under steady state and emergency hematopoiesis during immune response are orchestrated precisely by transcriptional networks formed by transcription factors (TFs) to direct multipotent progenitors into specific fate. TFs required for the development of single or multiple lineages within the hematopoietic system has been identified, such as Irf8 for type I classical dendritic cells …
Gut Reactions: Quantitative Predictions Of The Responses Of Human Gut Microbiota To Medical Interventions, Amy Elizabeth Langdon
Gut Reactions: Quantitative Predictions Of The Responses Of Human Gut Microbiota To Medical Interventions, Amy Elizabeth Langdon
Arts & Sciences Electronic Theses and Dissertations
The collection of microbes known as the human microbiome perform vital functions for their host, and when this community becomes unhealthy, its dysbiosis is implicated in a myriad of diseases. The gut microbiota in particular are known to suppress colonization of opportunistic pathogens, regulate the immune system, aid in nutrient breakdown, produce vitamins, and a growing number of other functions. In order to intervene in a dysbiotic microbial ecology, we can try to remove unwanted microbes or try to recolonize the gut with microbes expected to be beneficial. This dissertation provides an overview of the state of medical interventions for …
Retinal Ganglion Cells Underlying Visual Perception And Predation In Mice, Keith Patrick Johnson
Retinal Ganglion Cells Underlying Visual Perception And Predation In Mice, Keith Patrick Johnson
Arts & Sciences Electronic Theses and Dissertations
The spike trains of retinal ganglion cells (RGCs) are the sole source of visual information to the brain. In mice, more than 40 RGC types send signals to more than 50 brain areas. RGCs that perform nonlinear operations to extract specific visual features (e.g., the motion of an object against a background) are called feature detectors. Those that linearly integrate local changes in light inten-sity are known as pixel encoders. Most mouse RGC types are feature detectors. In the first part of my dissertation, I discovered a pixel encoder RGC type in mice, the PixON-RGC. I revealed how the unique …
A Novel Function Of Plasmacytoid Dendritic Cells In Regulating Type 2 Immune Responses, Hannah Leigh Miller
A Novel Function Of Plasmacytoid Dendritic Cells In Regulating Type 2 Immune Responses, Hannah Leigh Miller
Arts & Sciences Electronic Theses and Dissertations
The generation of an allergic response is particularly perplexing, as the mucosal immune system is exposed to a myriad of antigens on a daily basis, the majority of which do not elicit inflammation. However, for the growing population of patients impacted by allergic diseases, there is a clear breakdown of normal tolerance to innocuous antigens, resulting in symptoms mediated by antigen specific T helper 2 (Th2) cells. In addition to their well-established role in early antiviral immunity via production of type I interferon, plasmacytoid dendritic cells (pDC) have been implicated in the generation of immune tolerance in a variety of …