Immunopathology Commons^™

The Critical Role Of Nac1 In Triple-Negative Breast Cancer Stemness And Immunosuppression, Chrispus Ngule

Theses and Dissertations--Toxicology and Cancer Biology

Triple-negative breast cancer (TNBC) is a highly heterogeneous and the most lethal breast cancer (BC) subtype. We report here a new role of nucleus accumbens associated protein 1 (NAC1) in maintaining stemness signature and features of TNBC and controlling the status of myeloid-derived suppressor cells, which accounts for its role in tumor progression and metastasis. This report demonstrates increased NAC1 amplification in TNBC metastatic samples compared to nonmetastatic tissues. In vitro, NAC1 depletion in TNBC cells suppressed their proliferation, colony formation, migration, and invasion. In vivo, NAC1 knockdown in TNBC cells reduced tumorigenic ability, diminished tumor growth rate, and abolished …

Sphingosine Kinase 2 Depletion Dysregulates Hepatic Redox Metabolism And Enhances Inflammation In Early Metabolic Dysfunction-Associated Steatohepatitis (Mash), Kaitlyn Georgene Jackson

Theses and Dissertations

Metabolic dysfunction-associated steatotic liver disease (MASLD) currently affects one in three people worldwide; its prevalence is growing alongside other cardiometabolic disorders. Aberrations to redox and sphingolipid metabolism contribute to MASLD pathologic progression. Sphingosine-1-phosphate (S1P) is an active lipid, meaning that S1P participates in biochemical processes within the cell. S1P is generated by two distinct isoenzymes, sphingosine kinase (SphK)1 and SphK2. The localization of the SphK enzyme dictates S1P function. While cytosolic SphK1-generated S1P is well-characterized, nuclear and mitochondrial SphK2-generated S1P is less known. Moreover, SphK2 depletion effects on cellular redox processes and inflammation are not well-defined.

This study defines the …

The Role Of Hdac6 In Periodontal Inflammation, Hannah S. Lohner

Theses and Dissertations

Periodontal disease is a polymicrobial infection-induced chronic inflammatory disease and results in irreversible tissue damage and bone loss. While bacteria play a large role in the initiation of this disease, excessive and prolonged inflammatory immune responses are fundamental for its progression, making host directed therapy (HDT) a possible and potentially valuable treatment. Histone Deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from both histone and non-histone proteins, giving it a potential role in regulating inflammation initiated by pathogenic oral bacteria. Previous studies indicated that HDACs act as a bivalent regulator in inflammatory responses; however, the role that HDAC6 …

Role Of The Anti-Viral Immune Response In Neural Cell Modulation And Neurological Sequelae Of Childhood Viral Infections, Yashika Kamte

Electronic Theses and Dissertations

Viral infections of the central nervous system (CNS) often result in neurological sequelae and are considered a risk factor for the development of neurological disease. Moreover, the outcomes of a viral infection are largely dependent on the age of the host, with younger hosts developing more profound neuropathology. Perhaps the developing brain coupled with an immature immune system contributes to worse outcomes in the very young. Children suffering from brain infections are more prone to develop enduring neurological impairments even after recovery from the infection. Although majority of the brain growth occurs in utero, neurodevelopment continues throughout the juvenile …

The Effect Of Db1976 On The Fibrotic Response In Three-Spined Stickleback (Gasterosteus Aculeatus), Saif Quraishi

Honors Scholar Theses

The study of fibrosis in stickleback has been a growing field in which there have been a few studies conducted. This study examines two experiments involving the inhibition of fibrosis in stickleback. The first experiment used fish from the Kenai River Flats (KRF) in Alaska. The second experiment used fish from Roselle Lake in British Columbia, Canada. To determine the impact the drug had on fibrosis, sticklebacks from the KRF population were treated with DB1976 as well as alum, a pro‐inflammatory vaccine adjuvant that causes fibrosis (Kool et. al 2012). When each DB1976 + alum treatment group was compared with …

+Protective Roles For Interferon-Gamma In Astrocytes During Chronic Autoimmunity, Brandon C. Smith

ETD Archive

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS). Infiltrating inflammatory immune cells perpetuate demyelination and axonal damage in the CNS and significantly contribute to pathology and clinical deficits. Interferon (IFN)γ is classically described as deleterious in acute CNS autoimmunity, we and others have shown astrocytic IFNγ signaling also has a neuroprotective role. We found IFNγ signaling on astrocytes upregulates subunits of the immunoproteasome (iP) and programmed death ligand 1 (PD-L1), both of which serve protective roles during autoimmunity. Astrocyte-specific knockouts of Ifngr1 resulted in increased clinical severity in the MS murine model, experimental …

Cellular Mechanism Of Pentagalloyl Glucose-Mediated Prevention And Reversal Of Abdominal Aortic Aneurysms, Greg Halsey

All Dissertations

Abdominal aortic aneurysm (AAA) has been the 15th leading cause of death in persons older than 55 for the past ten years in several Western countries, with rupture resulting in an almost 100% mortality rate. AAA is a focal dilation of the aorta characterized by progressive loss of elastin and vascular smooth muscle cells (SMCs), as well as persistent inflammatory response [1]. The only treatment for AAA is surgery; however, the mortality post-procedure is still 1-4%, with a 15-30% chance of morbidity [2].

Pentagalloyl glucose (PGG) treatment is effective in the reversal of AAA. While its stabilizing interactions with extracellular …

Cytokine Data For Cytokine Profile Assessment From Peruvian Pinniped (Arctocephalus Australis And Otaria Byronia) Plasma, Mykenzee Munaco, Milton Levin, Michael Adkesson, Susana Cárdenas-Alayzad, Dimitrios G. Giarikos, Amy C. Hirons

SECLER Data

Large colonies of two vulnerable, sympatric pinniped species, Peruvian fur seals (Arctocephalus australis Peruvian subpopulation; PFS) and South American sea lions (Otaria byronia; SASL), reside and reproduce in Punta San Juan, Peru (PSJ) where they are exposed to stressors such as contaminants and El Niño Southern Oscillation (ENSO) events. The use of cytokines as immune biomarkers can be indicative of an animal’s health and function by allowing for the assessment of an individual's cytokine balance as type I helper T cells (Th1) or type II helper T cells (Th2) dominant. Utilizing archived pinniped plasma samples from 2009-2019 …

Complement System In Multiple Sclerosis: Its Role In Disease Course And Potential As A Therapeutic Target, Michael R. Linzey

Dartmouth College Ph.D Dissertations

Multiple sclerosis (MS) is a clinically heterogeneous neurological condition characterized by neuroinflammation and neurodegeneration. Relapsing-remitting MS, defined by inflammatory attacks, is the most common initial form of MS and there are currently 23 FDA-approved treatments for these patients. These therapies work primarily by reducing inflammation in the CNS; they do not work well in progressive disease. Therefore, an unmet medical need exists for effective therapeutic options to treat progressive MS (PMS).

In MS, intrathecal immunoglobulins synthesis (IIgS) correlates with disease progression. My goals for this dissertation were to establish the pathological role of IIgS and identify new potential therapeutic …

The Role Of Complement In Stroke And Traumatic Brain Injury, Christine Couch

MUSC Theses and Dissertations

Brain and neural injury are a non-specific disease category that includes traumatic brain injury (TBI) and stroke. Both TBI and stroke are common, costly, and leading causes of severe disability in adults. Both stroke and TBI are responsible for substantial disability in working age adults, with stroke being the second leading cause of death worldwide [1] and TBI a major cause of disability in people younger than their 40's [2]. The immune response after brain injury is multifactorial and involves both local and systemic events at the cellular and molecular level. The complement system is a component of both the …

Temporal, Phenotypic, And Quantitative Characterization Of Thyroid Infiltrating Mononuclear Cells During Development Of Spontaneous Autoimmune Thyroiditis In Obese Strain Chickens, Katelyn M. Clark

Poultry Science Undergraduate Honors Theses

The Obese strain (OS) of chickens spontaneously develops autoimmune thyroiditis and is a well-established biomedical model for Hashimoto’s thyroiditis in humans. Both conditions are characterized by the infiltration of the thyroid glands with mononuclear cells resulting in destruction of the thyroid tissue and impairment of the thyroid’s endocrinological functions. Past studies have described mononuclear cell infiltration in thyroids of the OS chickens, but the time-course, cell composition, and relative amounts of the various mononuclear cells infiltrating the thyroids has not been well defined. In this project, the mononuclear cell infiltrate was characterized phenotypically and quantitatively in OS chickens over the …

White Blood Cell Make Up In Kellback Snake Offspring Of Varying Maternal Size, Angelica Mccoy

Symposium of Student Scholars

The immune system is composed of various organs, systems, and other components with one of the most important being white blood cells. White blood cells are commonly separated into two scientific varieties, granulocytes and agranulocytes, which can be differentiated by the presence or absence of granules in the cytoplasm once stained on a slide. There are three granulocytes and two agranulocytes, each with a distinct function and shape. The ratio of these may impact the effectiveness of this portion of the immune system, and multiple factors could play a role in this ratio, an example being the size of an …

The Regulation Of Autoimmunity Genes In Pancreatic Β-Cells By Nf-Κb, Thomas Malone Martin

LSU Doctoral Dissertations

Type 1 diabetes (T1D) is an autoimmune disease where the immune system targets the pancreatic islet beta-cells, which are responsible for insulin production and secretion, leading to a state of insulin insufficiency. Many of the molecular details of disease onset and progression remain poorly understood, including key aspects of cytokine signaling. Therefore, we have examined some of the consequences of inflammatory cytokine signaling as a critical module relevant to T1D. Using interleukin-1 (IL-1) signaling as a well-defined paradigm for inflammation, we investigated key components of this signaling pathway in pancreatic beta-cells. We identified ICAM-1, one of the proteins expressed in …

Mir125a As Molecular Target Of Vitamin D Mediated Inhibition Of Cd4+ T Cell Differentiation Into Th17 Cells In Mrl/Lpr Lupus-Prone Mice, Miranda Hilt

Undergraduate Distinction Papers

The dynamic function of vitamin D in an array of immunomodulatory and anti-inflammatory mechanisms and its implication in the pathogenesis of autoimmune diseases has been the topic of much recent scholarship. Here I attempt to elucidate the molecular mechanism of vitamin D-mediated inhibition of the differentiation of CD4+ T cells into pro-inflammatory Th17 cells in MRL/lpr lupus prone mice by investigating how miR-125a expression is affected by dietary modulation of cholecalciferol (vitamin D₃). MRL/MpJ and MRL/lpr mice were split into three experimental groups and fed specially formulated diets that varied in their concentrations of vitamin D. …

The Immunomodulating Effects Of Delta-9 Tetrahydrocannabinol (Thc) And Cannabidiol (Cbd) In The Context Of Infection, Rose D. Goodman, Kate Rouse, Victor Jimenez

Annual Research Symposium

No abstract provided.

The Role Of Schwann Cells In Nerve Injury: Forskolin-Mediated Camp Activation Upregulates Tnfα Expression Despite Nf-Κb Downregulation In Lps-Treated Schwann Cells, Caitlyn E. Henry, Angela L. Asirvatham Ph.D.

Student Research Poster Presentations 2023

Although Schwann cells are known to play a role in axonal regeneration following nerve injury and inflammation, the exact mechanism is unknown. This study explores two potential mechanisms: the NF-κB and cAMP pathways. The NF-κB pathway produces cytokines, such as TNFα, to regulate inflammation, whereas the cAMP pathway is anti-inflammatory and regulates Schwann cell proliferation via AKAP95 and cyclin D3. Although it is well-known that NF-κB and cAMP are involved in inflammation, not much is known regarding the effects of forskolin-mediated cAMP activation on LPS-mediated NF-κB activation in Schwann cells. In this study, RT4-D6P2T immortalized rat Schwann cells were treated …

Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas

Graduate Theses/Dissertations

The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of …

Investigating The Relationship Between Metabolic Reprogramming And Peripheral Cd4+ T-Cell Inflammation In Human Type 2 Diabetes Pathogenesis, Gabriella Kalantar

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Chronic, low-grade systemic inflammation rises in obesity and promotes type 2 diabetes (T2D). Circulating immune cells are key indicators of obesity and T2D pathogenesis. T cells outnumber monocytes, in blood, suggesting that T cells might fuel peripheral inflammation in obesity/T2D. Our lab’s work supports this idea by identification of a Th17 cytokine profile in T2D from T-cell stimulated peripheral blood mononuclear cells. Work described herein further supported this work by demonstrating that T cells dominate peripheral inflammation over monocytes across the spectrum of obesity and glycemic control. Our lab has also recently shown that inflammation changes during prediabetes (preT2D), identified …

Vitamin D Enhanced Vitamin D Receptor (Vdr) Inhibition Of Nlrp3 Inflammasome Activation Can Attenuate The Development Of Autoimmune Thyroiditis, Alexzon Mandac

Capstone Showcase

Autoimmune Thyroiditis (AIT) is a prevalent autoimmune disease affecting approximately 2% of the population. Characterized by the gradual loss of thyroid function through an autoimmune attack on the thyroid gland, the disease manifests symptoms that negatively affect one’s quality of life. The mechanisms behind the disease’s pathophysiology are not fully understood; however, researchers are examining the involvement of the NLRP3 inflammasome in the disease. This thesis will address the question of whether Vitamin D can act as an inhibitor of the NLRP3 inflammasome and attenuate the progression of AIT in mouse model. Current investigations explore the effects of NLRP3 inhibition …

Cluster Homolog Of Immunoglobulin-Like Receptor Genes In Chicken Immune Responses, Brandi A. Sparling

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation explores the identity and role of immunoglobulin-like (Ig-like) receptors in chickens, with focus on their implications in disease and disease progression. These receptors, wisely expressed across immune cells, interact with the major histocompatibility complex (MHC) class I molecules to modulate immune responses in mammals. Due to the insufficient representation of chicken Ig-like receptors in online databases, this study systematically annotates the chicken Cluster Homolog of Immunoglobulin-like Receptors (CHIR) genes using advanced bioinformatic techniques, aligning with the release of the 7th edition of the chicken genome assembly that comprises builds for a broiler and layer chicken. The analysis identifies …