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Full-Text Articles in Cell and Developmental Biology

Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells, Taylor Chrisikos Dec 2021

Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells, Taylor Chrisikos

Dissertations & Theses (Open Access)

Conventional dendritic cells (cDCs) are an essential immune population, responsible for controlling adaptive immunity and tolerance. Recently, type I cDCs (cDC1s) have been delineated as a distinct cDC subset, uniquely responsible for coordinating T cell-mediated immunity against pathogens and tumors. Although the importance of cDC1s is now well established, the mechanisms that regulate cDC1 function remain largely unknown. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of interleukin 10 (IL-10), an immunosuppressive cytokine. Therefore, we hypothesized that STAT3 and IL-10 inhibit cDC1 function and induction of T cell-mediated immunity. Herein, we show that IL-10 inhibits polyinosinic:polycytidylic …


Development Of In Vitro Models To Study The Rapid Extraintestinal Dissemination Of Salmonella., Adarsh Gopinath May 2020

Development Of In Vitro Models To Study The Rapid Extraintestinal Dissemination Of Salmonella., Adarsh Gopinath

Electronic Theses and Dissertations

Salmonella appears in the bloodstream of mice in as little as 15 minutes after oral inoculation and establishes persistent colonies in the spleen and liver. While its pathway to blood is undetermined, this phenomenon is dependent on the activity of Salmonella pathogenicity island 2 (SPI-2) coded type III secretion system (T3SS) and CD18+ phagocytes. We hypothesize that dendritic cells associated with the basal face of the gut epithelium, that are naturally migratory and known to sample for luminal antigens directly transport Salmonella to the bloodstream. This process comprises of at least two phases, dissociation and reverse transmigration. We define dissociation …


Understanding The Transcriptional Mechanisms Underlying Dendritic Cell Development, Prachi Bagadia Aug 2019

Understanding The Transcriptional Mechanisms Underlying Dendritic Cell Development, Prachi Bagadia

Arts & Sciences Electronic Theses and Dissertations

Dendritic cells (DCs) comprise an important immune lineage that plays a critical role in initiating and sustaining the proper immune response. They can be divided into two distinct branches, classical/conventional DCs (cDCs) or plasmacytoid DCs (pDCs). cDCs can further be classified as cDC1 or cDC2. Each DC subset exerts unique functions in vivo and are necessary for a complete immune response. The precise transcriptional programs underlying DC specification and commitment remain unclear. cDC1, cDC2, and pDC all arise from the common DC progenitor (CDP) in the bone marrow. How the CDP gives rise to all three DC subsets in an …


The Trophic Life Cycle Stage Of The Opportunistic Fungal Pathogen Pneumocystis Murina Hinders The Ability Of Dendritic Cells To Stimulate Cd4+ T Cell Responses, Heather M. Evans, Andrew Simpson, Shu Shen, Arnold J. Stromberg, Carol L. Pickett, Beth A. Garvy Oct 2017

The Trophic Life Cycle Stage Of The Opportunistic Fungal Pathogen Pneumocystis Murina Hinders The Ability Of Dendritic Cells To Stimulate Cd4+ T Cell Responses, Heather M. Evans, Andrew Simpson, Shu Shen, Arnold J. Stromberg, Carol L. Pickett, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage induces proinflammatory immune responses, while trophic forms suppress the cytokine response to multiple pathogen-associated molecular patterns (PAMPs), including β-glucan. A targeted gene expression assay was used to evaluate the dendritic cell response following stimulation with trophic forms alone, with a normal mixture of trophic forms and cysts, or with β-glucan. We demonstrate that stimulation with trophic forms downregulated the expression of multiple genes normally associated with the response to infection, including genes encoding …


Haematopoietic Stem Cells In Spleen Have Distinct Differentiative Potential For Antigen Presenting Cells., Jonathan Tan, Helen O'Neill Sep 2015

Haematopoietic Stem Cells In Spleen Have Distinct Differentiative Potential For Antigen Presenting Cells., Jonathan Tan, Helen O'Neill

Jonathan Tan

Dendritic cells (DC) are known to develop from macrophage dendritic progenitors (MDP) in bone marrow (BM), which give rise to conventional (c)DC and monocytes, both dominant antigen presenting cell (APC) subsets in spleen. This laboratory has however defined a distinct dendritic-like cell subset in spleen (L-DC), which can also be derived in long-term cultures of spleen. In line with the restricted in vitro development of only L-DC in these stromal cultures, we questioned whether self-renewing HSC or progenitors exist in spleen with restricted differentiative capacity for only L-DC. Neonatal spleen and BM were compared for their ability to reconstitute mice …


Immune Recognition Of Self Nucleic Acids Driven By Endogenous Antimicrobial Peptides: Role In Autoimmunity, Dipyaman Ganguly Aug 2010

Immune Recognition Of Self Nucleic Acids Driven By Endogenous Antimicrobial Peptides: Role In Autoimmunity, Dipyaman Ganguly

Dissertations & Theses (Open Access)

Innate immune recognition of extracellular host-derived self-DNA and self-RNA is prevented by endosomal seclusion of the Toll-like receptors (TLRs) in the dendritic cells (DCs). However, in psoriasis plasmacytoid dendritic cells have been found to be able to sense self-DNA molecules in complex with the endogenous cationic antimicrobial peptide LL37, which are internalized into the endosomal compartments and thus can access TLR9. We investigated whether this endogenous peptide can also interact with extracellular self-RNA and lead to DC activation. We found that LL37 binds self-RNA as well as self-DNA going into an electrostatic interaction; forms micro-aggregates of nano-scale particles protected from …


Haematopoietic Stem Cells In Spleen Have Distinct Differentiative Potential For Antigen Presenting Cells., Jonathan Tan, Helen O'Neill Dec 2009

Haematopoietic Stem Cells In Spleen Have Distinct Differentiative Potential For Antigen Presenting Cells., Jonathan Tan, Helen O'Neill

Helen O'Neill

Dendritic cells (DC) are known to develop from macrophage dendritic progenitors (MDP) in bone marrow (BM), which give rise to conventional (c)DC and monocytes, both dominant antigen presenting cell (APC) subsets in spleen. This laboratory has however defined a distinct dendritic-like cell subset in spleen (L-DC), which can also be derived in long-term cultures of spleen. In line with the restricted in vitro development of only L-DC in these stromal cultures, we questioned whether self-renewing HSC or progenitors exist in spleen with restricted differentiative capacity for only L-DC. Neonatal spleen and BM were compared for their ability to reconstitute mice …


Dendritic Cells As Immune Regulators: The Mouse Model, Kristin Griffiths, Helen O'Neill Dec 2007

Dendritic Cells As Immune Regulators: The Mouse Model, Kristin Griffiths, Helen O'Neill

Helen O'Neill

Dendritic cells (DC) are central to the immune system because of their role in antigen presentation leading to either tolerance or immunity among cells of the adaptive immune response. It is becoming increasingly evident that DC show extensive plasticity in terms of their origin and function, giving rise to a number of subsets represented differentially in all lymphoid organs. This article considers the tolerogenic capacity of murine DC and draws a distinction between DC that induce tolerance in the immature state and immunity in an inflammatory context, and those that act as regulatory cells inducing immunosuppression in the presence of …


The Immunogenicity Of Dendritic Cell-Derived Exosomes, Ben Quah, Helen O'Neill Dec 2004

The Immunogenicity Of Dendritic Cell-Derived Exosomes, Ben Quah, Helen O'Neill

Helen O'Neill

Exosome production represents an alternate endocytic pathway for secretion. Multivesicular endosomes (MVE) fuse with the plasma membrane expelling internal vesicles or exosomes from cells. Exosome production has been recently described for immune cells including B cells, dendritic cells (DC), mast cells, macrophages and T cells. Exosomes derived from some DC populations stimulate T lymphocyte proliferation in vitro and have potent capacity to generate anti-tumour immune responses in vivo. These reported studies have involved in vitro grown mature DC expanded from precursors with cytokines. However, immature DC produce higher numbers of exosomes than mature DC and this is thought to be …