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Immunology and Infectious Disease
Washington University in St. Louis
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- Immunotherapy (5)
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- Dendritic cells (3)
- Inflammation (3)
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- Host-pathogen interactions (2)
- IL-10 (2)
- Immunity (2)
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- Memory B cell (2)
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Articles 1 - 30 of 74
Full-Text Articles in Life Sciences
Tissue Resident Macrophages Drive Fibrosis During Pancreas Inflammatory Injury And Pancreatic Ductal Adenocarcinoma, John Baer
Arts & Sciences Electronic Theses and Dissertations
The immune system, and especially macrophages, are central in responding to infections, as well as providing a wide array of functions in other pathologies, especially in responding to inflammation. It is established that macrophages will accumulate within tissues during inflammation, many times secreting cytokines and chemokines central to the inflammatory response. This is particularly true during pancreatitis, or inflammation of the pancreas, where it has been shown that macrophages and monocytes accumulate in the pancreas to have various roles in further promoting inflammation. It is not well established, however, whether there are divergent roles for the distinct macrophage subsets that …
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 …
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. …
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 …
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 …
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 …
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 …
Transcriptional Control Of Dendritic Cell Function And Development, David Alexander Anderson Iii
Transcriptional Control Of Dendritic Cell Function And Development, David Alexander Anderson Iii
Arts & Sciences Electronic Theses and Dissertations
Dendritic cells (DCs) are innate immune cells of the myeloid lineage that are specialized at pathogen recognition, cytokine production, and antigen presentation. Their functions and developmental pathways are largely conserved between mice and humans and mice. The DC lineage is composed of two major subsets, known as plasmacytoid DCs (pDCs) and classical DCs (cDCs). Research conducted to date suggests that the function of pDCs, limited to viral antigen recognition and type I interferon production, can be compensated by other immune cell lineages. On the other hand, there is a consensus that diversified subsets cDCs in mice and humans are essential …
The Roles Of Capsular Polysaccharides And Diet In The Immune Response To A Bacteroides Thetaiotaomicron Antigen, Samantha Hsieh
The Roles Of Capsular Polysaccharides And Diet In The Immune Response To A Bacteroides Thetaiotaomicron Antigen, Samantha Hsieh
Arts & Sciences Electronic Theses and Dissertations
The environment is well recognized to modulate immune responses within the intestinal mucosa in a general fashion. However, the connection between the effects of the environment on the immune response directed towards specific intestinal microbes is unclear. Progress in this area has been hampered by the lack of a model system in which the immune responses to a specific antigen in a gut symbiont can be examined. To this end, we developed a novel CD4+ T cell model, termed BθOM, that is specific for a dominant antigen in the gut symbiont Bacteroides thetaiotaomicron (B. theta). In this work, we use …
Etv2/Myct1 Axis In The Regulation Of Tumor Angiogenesis And Anti-Tumor Immunity, Ashraf Ul Kabir
Etv2/Myct1 Axis In The Regulation Of Tumor Angiogenesis And Anti-Tumor Immunity, Ashraf Ul Kabir
Arts & Sciences Electronic Theses and Dissertations
Angiogenesis is a critical determinant of neoplastic growth and metastatic spread. As such, anti-angiogenic approaches have long been tried to throttle down tumor progression. However, current anti-angiogenic treatments so far have produced modest clinical benefits. Further in-depth research has provided rationales behind these disappointing and apparent perplexing clinical outcomes. It is now established that VEGF (vascular endothelial growth factor) and other prominent current angiogenic targets are neither specific to the vascular system nor the pathological conditions explaining the sub-optimal angiogenic control following the existing treatments. This suggests that anti-angiogenesis could still be a viable strategy for cancer patients should there …
Regulation Of Gut Commensal-Specific T Cell Differentiation By Dendritic Cell Subsets, Emilie Russler-Germain
Regulation Of Gut Commensal-Specific T Cell Differentiation By Dendritic Cell Subsets, Emilie Russler-Germain
Arts & Sciences Electronic Theses and Dissertations
The mammalian gastrointestinal tract can harbor both beneficial commensal organisms important for host health, but also pathogenic organisms capable of intestinal damage. It is therefore important that the host immune system mounts appropriate responses to different intestinal organisms – promoting tolerance to some, controlling the colonization of others, and inducing sterilizing immunity in cases of noxious pathogens. Failure to induce tolerance to commensal organisms may underlie immune-mediated diseases such as human inflammatory bowel disease, while inappropriate tolerance to more harmful organisms has the potential to result in infection, inflammation, or even malabsorption. Adaptive immune responses to intestinal commensal organisms are …
Glial Inflammatory Responses Regulate Neurocognitive Recovery Following Viral Encephalitis, Allison Luen Soung
Glial Inflammatory Responses Regulate Neurocognitive Recovery Following Viral Encephalitis, Allison Luen Soung
Arts & Sciences Electronic Theses and Dissertations
The concept of the brain as an immune privileged organ has been slowly shifting as an in-creasing number of studies have demonstrated that even under homeostatic conditions, commu-nication between the nervous and immune system is essential for proper brain function. Given their roles in innate and adaptive immunity, glial cells and infiltrating immune cells have been placed at the center of this communication axis. Microglia, astrocytes, and T cells have all been shown to receive and convey information to all neural cell types in a coordinated effort to re-spond to injury and infection and initiate reparative mechanisms as well as …
Mechanisms Of Natural Killer Cell Anti-Tumor Function And Homeostasis, Julia Alexandra Wagner
Mechanisms Of Natural Killer Cell Anti-Tumor Function And Homeostasis, Julia Alexandra Wagner
Arts & Sciences Electronic Theses and Dissertations
Natural killer (NK) cells are innate lymphoid cells (ILCs) that mediate anti-tumor and anti-viral immune responses. They do so via two primary effector functions: cytokine production and direct cytotoxicity. Unlike adaptive T and B lymphocytes, NK cells do not rearrange their DNA to express a predominant antigen-specific receptor, and instead express a variety of stochastically-expressed, germline DNA-encoded activating and inhibitory receptors whose signals integrate to govern their functional responses. What results is a diverse repertoire of NK cells capable of recognizing a variety of malignantly-transformed or virally-infected cells. Studies from several groups have established the anti-tumor potential of NK cells, …
Examining Early Interactions Between Innate Airway Resident Immune Cells And Mtb-Specific Factors During Pulmonary Infection With Mycobacterium Tuberculosis, Micah D. Dunlap
Arts & Sciences Electronic Theses and Dissertations
Mycobacterium tuberculosis (Mtb) is the leading cause of death by an infectious agent in the world today, infecting roughly one quarter of humans. Despite this, the mechanisms of early pathogenesis and host protective innate immune responses remain poorly understood and uncharacterized.
Lung resident Alveolar Macrophages (AMs) are the first host contact with Mtb bacilli after inhalation and are thus key mediators of the early pulmonary immune response. AMs are generally believed to reside entirely in the airway, but it was recently demonstrated that they have the capacity to egress and enter into granulomas during pulmonary infection with hypervirulent Mtb. Furthermore, …
Homeostatic T Cell Receptor Interactions With Self-Peptide Tune Cd4+ T Cell Function, Juliet Marie Bartleson
Homeostatic T Cell Receptor Interactions With Self-Peptide Tune Cd4+ T Cell Function, Juliet Marie Bartleson
Arts & Sciences Electronic Theses and Dissertations
Homeostatic T Cell Receptor Interactions with Self-Peptide Tune CD4+ T Cell Function
by
Juliet Marie Bartleson
Doctor of Philosophy in Biology and Biomedical Sciences
Immunology
Washington University in St. Louis, 2021
Professor Paul M. Allen, Chair
Mature CD4+ T cells circulate throughout peripheral secondary lymphoid organs using their T cell receptor (TCR) to surveil peptide presented on major histocompatibility complex class II molecules (pMHC) in search of cognate, antigenic peptide. In the absence of an immune challenge, however, the TCR is continuously interacting with self-pMHC, which induces a relatively weak TCR signal known as tonic signaling. These homeostatic TCR:self-pMHC interactions …
Protein Synthesis Adaptation To The Au-Rich Transcriptome Of Plasmodium Falciparum, Jessey Lee Erath
Protein Synthesis Adaptation To The Au-Rich Transcriptome Of Plasmodium Falciparum, Jessey Lee Erath
Arts & Sciences Electronic Theses and Dissertations
The process of protein synthesis whereby a messenger RNA is decoded into an amino acid chainis conserved among the domains. Fastidious protein synthesis is necessary for organism survival. However, exceptions negatively affecting the mRNA translation cycle – inadvertently or by design – may occur. Polyadenosine tracts are one such motif causing ribosomal stalling and frameshifting in almost all organisms tested thus far; save Plasmodium spp. Thus, with ~60% of their protein-coding genome harboring polyadenosine tracts, the elucidation of such paradigm-breaking adaptations enabling Plasmodium spp. to translate this typically problematic motif without issue is salient from both basic science and clinical …
The Roles Of Plasmepsins Ix And X In Malaria Parasite Biology, Armiyaw Sebastian Nasamu
The Roles Of Plasmepsins Ix And X In Malaria Parasite Biology, Armiyaw Sebastian Nasamu
Arts & Sciences Electronic Theses and Dissertations
Proteases of the malaria parasite Plasmodium falciparum have been targeted for drug discovery for decades. The P. falciparum genome encodes ten aspartic proteases called plasmepsins, which are involved in diverse cellular processes. In this work we address the roles of two of these plasmepsins, plasmepsins IX and X (PM IX and X), the two least studied aspartic proteases in blood stage malaria parasites till date. We explore the essentiality of these proteases in parasite development, attempt to identify their substrates and the ability to drug them. We show that PM IX is essential for erythrocyte invasion, acting on rhoptry secretory …
A Mechanistic And Genomic Analysis Of Molluscum Contagiosum Virus Immune Evasion, Ian Benjamin Harvey
A Mechanistic And Genomic Analysis Of Molluscum Contagiosum Virus Immune Evasion, Ian Benjamin Harvey
Arts & Sciences Electronic Theses and Dissertations
Molluscum contagiosum virus (MCV) is a common human-specific poxvirus with a proclivity for
infecting children and the immune-compromised. A characteristic MCV infection is restricted to
the epidermal layers of the skin and can persist for weeks to years in an otherwise healthy
individual. The high clinical burden of MCV is at odds with our limited knowledge regarding how
it successfully evades the human immune response, which is in part due to the lack of an animal
model or cell line to propagate the virus. Through this dissertation, we have uncovered and
characterized a novel mechanism by which MC80, a protein …
Mechanisms Of Sting-Associated Vasculopathy And Immunodeficiency, Brock Gordon Bennion
Mechanisms Of Sting-Associated Vasculopathy And Immunodeficiency, Brock Gordon Bennion
Arts & Sciences Electronic Theses and Dissertations
STING N153S in mice and STING N154S in humans cause spontaneous autoimmunity. Specifically, these mutations reduce the numbers of T cells and NK cells, and cause lung disease. However, mice develop perivascular lung inflammation that is distinct from the pulmonary fibrosis observed in human patients. Viral infections are known to exacerbate autoimmunity and foment pulmonary fibrosis. Therefore, we hypothesized that exposure to a virus may influence STING N153S disease in mice. To test this, we infected STING N153S animals with the gammaherpesvirus family member, gHV68, and found that 14 days post infection pulmonary fibrosis was readily observed by histological staining. …
Mechanisms Of Cross-Presentation By Cdc1s, Derek James Theisen
Mechanisms Of Cross-Presentation By Cdc1s, Derek James Theisen
Arts & Sciences Electronic Theses and Dissertations
Classical dendritic cells (cDCs) are specialized antigen presenting cells that can be divided into distinct subsets based on the types of pathogens they respond to and the type of immune response they generate. The cDC1 subset is specialized in priming CD8 T cell responses through the process of cross-presentation. During cross-presentation, exogenous protein antigens are taken up by cDC1 and presented on MHCI molecules, allowing for the priming of CD8 T cells during conditions when DCs themselves are not directly infected. The ability to cross-present in vivo is unique to cDC1, and is essential for anti-viral responses and rejection of …
Epigenetic And Signaling Pathways Regulating The Maintenance Of Cd8 T Cell Identity And Function, Daniel Verbaro
Epigenetic And Signaling Pathways Regulating The Maintenance Of Cd8 T Cell Identity And Function, Daniel Verbaro
Arts & Sciences Electronic Theses and Dissertations
In response to infection, antigen specific CD4 and CD8 T cells rapidly divide to provide help to the immune system and promote cytotoxicity of infected cells, respectively. Through this rapid division, CD4 and CD8 T cells maintain silencing of the opposing lineage’s genes, which is essential to acutely eliminating pathogens. However, not all pathogens are acutely eliminated even when silencing is maintained, and the pathogen persists in the presence of activated CD8 T cells. CD8 T cells chronically exposed to antigen are phenotypically different than CD8 T cells acutely exposed to antigen, but CD8 T cell still exert control over …
Cognitive Recovery In The Post-Infectious Cns, Charise Joy Garber
Cognitive Recovery In The Post-Infectious Cns, Charise Joy Garber
Arts & Sciences Electronic Theses and Dissertations
Neuroinflammation plays a pivotal role in a variety of diseases of the CNS associated with cognitive impairment, including Alzheimerճ Disease, Parkinsonճ Disease with dementia, Multiple Sclerosis, anti-NMDA receptor encephalitis, and West Nile Virus Neuroinvasive disease (WNND). Despite strong evidence that infiltration of peripheral immune cells and activation of resident microglia and astrocytes occurs in these various diseases, very little is known about how this altered immune environment may influence normal cognitive function. Given that communication between the nervous and immune system is essential for normal cognitive function, the central motivation of my thesis work is to understand the mechanisms by …
In Vivo Mechanisms Of Natural Killer Cell Tolerance, Michael Bern
In Vivo Mechanisms Of Natural Killer Cell Tolerance, Michael Bern
Arts & Sciences Electronic Theses and Dissertations
Natural killer (NK) cells are cytotoxic innate immune cells that provide protection from pathogens and tumors. To carry out these functions, NK cells must distinguish between healthy and unhealthy self-cells. Inability to recognize stressed cells would lead to a failure of NK-cell immunity whereas inability to identify healthy cells could lead to NK-cell autoimmunity. It remains unclear, however, how NK cells are able to distinguish healthy and unhealthy self-cells with a limited repertoire of germline-encoded receptors. The "missing-self" hypothesis proposes that NK cells identify stressed cells by their reduced expression of MHC class I (MHC-I) that is almost ubiquitously expressed …
Dendritic Cell Development And Function, Vivek Durai
Dendritic Cell Development And Function, Vivek Durai
Arts & Sciences Electronic Theses and Dissertations
Dendritic cells (DCs) are a group of immune cells that include both classical dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs). cDCs are further comprised of two distinct subsets, cDC1s and cDC2s, which play critical roles in the initiation of innate and adaptive immune responses. Understanding how these lineages develop and function is therefore paramount. All DCs require the receptor tyrosine kinase Flt3 and its ligand Flt3L for their development, but the loss of Flt3L in mice leads to a more severe DC deficiency than does the loss of Flt3. This has led to speculation that Flt3L can bind to …
Signaling Mechanisms In Adaptive Immunity, Saravanan Raju
Signaling Mechanisms In Adaptive Immunity, Saravanan Raju
Arts & Sciences Electronic Theses and Dissertations
The adaptive immune response consists of interplay between CD4 T cells, CD8 T cells, and B cells which function in control of pathogen in the host. T cells responding via their TCR express cytokines and costimulatory molecules that support direct effector activity and also promote high-affinity antibody generation through augmenting of B cell responses. However, the molecular components that contribute T cell function to balance viral control and the potential for host damage are incompletely understood. In this work, we establish a role for the adaptor molecule CD2AP in modulation of CD4 T cell responses to chronic LCMV infection in …
Regulation And Function Of Trem2-Dependent Pathways In Neurodegeneration, Wilbur Madison Song
Regulation And Function Of Trem2-Dependent Pathways In Neurodegeneration, Wilbur Madison Song
Arts & Sciences Electronic Theses and Dissertations
Carriers of the R47H allele of the microglia-specific lipid receptor TREM2 have a greatly increased risk of developing Alzheimerճ disease. The objective of this dissertation is to develop further mechanistic knowledge about how TREM2 is regulated and how TREM2 mutations affect microglia and neurodegeneration. Using an in vitro reporter assay, we find that several AD risk-associated TREM2 mutations decrease ligand-dependent activation. Using humanized TREM2 mice, we find that in vivo, the R47H mutation leads to reduced microglia activation and response to A_, as well as decreased shedding of soluble TREM2. These results suggest that TREM2 is protective during disease. We …