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You searched for +publisher:"University of North Carolina" +contributor:("Plevy, Scott E."). Showing records 1 – 2 of 2 total matches.

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University of North Carolina

1. Steinbach, Erin Cathleen. Macrophage phosphoinositide 3-kinase p110δ regulates intestinal homeostasis by directing adaptive immunity and enhancing microbial clearance.

Degree: Microbiology and Immunology, 2013, University of North Carolina

The human inflammatory bowel diseases (IBDs), Crohn’s disease (CD) and ulcerative colitis, result from an inappropriately directed immune response to enteric microbiota in a genetically susceptible host. IBDs represent an increasing burden on the global health care system, as incidence is increasing and effective therapies remain elusive. Genome-wide association studies highlight the importance of host innate immune cell-microbial interactions in the pathogenesis of IBDs. PI3K signaling regulates diverse functions, including cell growth, differentiation, proliferation and survival. The Class IA PI3K catalytic subunit p110δ negatively regulates toll-like receptor signaling in innate immune cells. The importance of p110δ in intestinal homeostasis is shown in a mouse harboring a kinase-dead p110δ (p110δKD) that develops spontaneous Th1/Th17-skewed colitis. We describe a requirement for the enteric microbiota to drive intestinal inflammation in p110δKD mice. Microbial-innate immune interactions maintain homeostasis through regulation of both protective (IL-10) and inflammatory (IL-12p40) cytokines, and p110δ is a central regulator of this balance. Additionally, p110δ positively regulates eradication of intracellular bacteria in macrophages. Persistence of intracellular bacteria and chronic stimulation in intestinal p110δKD macrophages propagates the cytokine imbalance. Furthermore, p110δ orchestrates innate immune cell regulation of pathogenic adaptive immune responses. Importantly, in human CD, decreased intestinal PIK3CD gene expression and an inverse correlation with intestinal IL12B:IL10 ratios are demonstrated. Thus, p110δ appears to be a central homeostatic switch in the intestine, governing the critical balance between IL- 12/23 and IL-10 induced by the microbiota that determines the subsequent T cell response. Counter to prevailing paradigms where p110δ inhibition is a strategic approach in inflammatory diseases, strategies to induce p110δ gene expression could be a potential therapeutic approach in human IBDs. Advisors/Committee Members: Steinbach, Erin Cathleen, Plevy, Scott E., University of North Carolina at Chapel Hill.

Subjects/Keywords: School of Medicine; Department of Microbiology and Immunology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Steinbach, E. C. (2013). Macrophage phosphoinositide 3-kinase p110δ regulates intestinal homeostasis by directing adaptive immunity and enhancing microbial clearance. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:4264d9c2-8a74-447c-8e6d-a692549ce860

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Steinbach, Erin Cathleen. “Macrophage phosphoinositide 3-kinase p110δ regulates intestinal homeostasis by directing adaptive immunity and enhancing microbial clearance.” 2013. Thesis, University of North Carolina. Accessed October 31, 2020. https://cdr.lib.unc.edu/record/uuid:4264d9c2-8a74-447c-8e6d-a692549ce860.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Steinbach, Erin Cathleen. “Macrophage phosphoinositide 3-kinase p110δ regulates intestinal homeostasis by directing adaptive immunity and enhancing microbial clearance.” 2013. Web. 31 Oct 2020.

Vancouver:

Steinbach EC. Macrophage phosphoinositide 3-kinase p110δ regulates intestinal homeostasis by directing adaptive immunity and enhancing microbial clearance. [Internet] [Thesis]. University of North Carolina; 2013. [cited 2020 Oct 31]. Available from: https://cdr.lib.unc.edu/record/uuid:4264d9c2-8a74-447c-8e6d-a692549ce860.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Steinbach EC. Macrophage phosphoinositide 3-kinase p110δ regulates intestinal homeostasis by directing adaptive immunity and enhancing microbial clearance. [Thesis]. University of North Carolina; 2013. Available from: https://cdr.lib.unc.edu/record/uuid:4264d9c2-8a74-447c-8e6d-a692549ce860

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of North Carolina

2. Sheikh, Shehzad Zafar. Defects in Macrophage Specific Homeostatic Pathways in the Inflammatory Bowel Diseases.

Degree: Microbiology and Immunology, 2010, University of North Carolina

Intestinal macrophages are specialized to carry out their functions in the local antigen- and microbiota-rich environment. They are refractory to the induction of proinflammatory cytokines, yet still display potent phagocytic and bactericidal activity. These adaptations allow the intestinal macrophage to eradicate microbes that breach the intestinal epithelial barrier while maintaining local tissue homeostasis. The inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, results from an inappropriately directed inflammatory response to the enteric microbiota in a genetically susceptible host. In contrast to the characteristic anti-inflammatory phenotypic and functional profile of normal intestinal macrophages, these macrophages react to luminal microbes and become potent producers of proinflammatory cytokines such as IL-12 family members. IL-12 and 23 are heterodimeric cytokines produced by macrophages and dendritic cells that are important bridges between innate and adaptive immunity. Although the molecular events that lead to the expression of IL-12 and Il-23 in macrophages through TLR signaling have been well defined, anti-inflammatory pathways that lead to inhibition of these cytokines in macrophages have not been fully elucidated. We identify two important homeostatic pathways; IFN-γ and HO-1 that regulate enteric microbiota-induced production of IL-12 and 23 by macrophages. IFN-γ inhibits TLR induced IL-23 expression in macrophages, and these events prevent the initiation and progression of spontaneous IL-23-driven experimental colitis in IL-10 deficient (IL-10-/-) mice. Moreover, we demonstrate that enteric microbiota-induced heme-oxygenase 1 (HO- 1) is critical in the prevention of experimental colitis, through inhibition of IL-12 family members and augmentation of macrophage microbicidal pathways. In our first study we demonstrate that IFN-γ has anti-inflammatory properties in murine models of Th1/Th17 mediated experimental colitis through attenuation of TLRmediated IL-23 expression in macrophages. In the second series of experiments, using germ-free WT and colitis-prone IL-10-/- mice we show that intestinal HO-1 expression induced by the enteric microbiota is an important homeostatic pathway. We also identify signaling pathways (MyDD88, MAPK and Pi3K) essential for HO-1 induction in macrophages. Finally, in our third study, protective effects of the HO-1 pathway were determined in Th2-mediated chronic colonic inflammation in T cell receptor- alpha (TCRα) deficient (-/-) mice. TCRα-/- mice exposed to carbon monoxide (CO) or treated with a pharmacologic HO-1 inducer demonstrated significant amelioration of active colitis. We demonstrate that HO-1 regulates mucosal innate immune responses in the TCRα-/- mouse through IL-10 induction in colonic macrophages. Advisors/Committee Members: Sheikh, Shehzad Zafar, Plevy, Scott E., University of North Carolina at Chapel Hill.

Subjects/Keywords: School of Medicine; Department of Microbiology and Immunology

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Sheikh, S. Z. (2010). Defects in Macrophage Specific Homeostatic Pathways in the Inflammatory Bowel Diseases. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:e9f3f872-ae20-4d52-b298-16b98164daa8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Sheikh, Shehzad Zafar. “Defects in Macrophage Specific Homeostatic Pathways in the Inflammatory Bowel Diseases.” 2010. Thesis, University of North Carolina. Accessed October 31, 2020. https://cdr.lib.unc.edu/record/uuid:e9f3f872-ae20-4d52-b298-16b98164daa8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Sheikh, Shehzad Zafar. “Defects in Macrophage Specific Homeostatic Pathways in the Inflammatory Bowel Diseases.” 2010. Web. 31 Oct 2020.

Vancouver:

Sheikh SZ. Defects in Macrophage Specific Homeostatic Pathways in the Inflammatory Bowel Diseases. [Internet] [Thesis]. University of North Carolina; 2010. [cited 2020 Oct 31]. Available from: https://cdr.lib.unc.edu/record/uuid:e9f3f872-ae20-4d52-b298-16b98164daa8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sheikh SZ. Defects in Macrophage Specific Homeostatic Pathways in the Inflammatory Bowel Diseases. [Thesis]. University of North Carolina; 2010. Available from: https://cdr.lib.unc.edu/record/uuid:e9f3f872-ae20-4d52-b298-16b98164daa8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.