[{"key":"dc.contributor.author","value":"Shim, Yaein Amy","language":null},{"key":"dc.date.accessioned","value":"2020-05-04T21:07:13Z","language":null},{"key":"dc.date.available","value":"2021-04-30T07:00:00Z","language":null},{"key":"dc.date.issued","value":"2020","language":"en"},{"key":"dc.identifier.uri","value":"http:\/\/hdl.handle.net\/2429\/74321","language":null},{"key":"dc.description.abstract","value":"The immune system plays a crucial role in the protection of the host against infection and the maintenance of homeostasis under normal conditions. This is achieved by cooperative work amongst a diverse population of immune cells. The pan-leukocyte marker CD45 is a receptor-type tyrosine phosphatase expressed on all nucleated hematopoietic cells. While the function of CD45 on adaptive immune cells has been well described, the role of CD45 on innate immune cells and erythroid progenitors is less understood.\r\nCD71\u207aTER119\u207a erythroid progenitors are prevalent in neonates; in addition to generating mature erythrocytes, they create an immunosuppressive environment. Here, I show that CD45 regulates late erythroid development as CD45-deficient mice maintained a high level of CD71\u207aTER119\u207a progenitor cells in the spleen into adulthood. Despite the increase, CD45-deficient mice had normal numbers of mature red blood cells (RBCs) due to increased sensitivity of erythroid progenitors to erythropoietin (EPO) and an increased number of EPO-producing red pulp macrophages (RPMs). Increased CD71\u207aTER119\u207a cells in CD45-deficient RAGKO mice (CD45RAGKO) had an impact on the outcome of T cell transfer colitis. CD45RAGKO had delayed systemic wasting and reduced TNF\u03b1 production by splenic myeloid cells despite having an equal level of inflammation in the colon. Adoptive transfer of erythroid progenitors from CD45RAGKO donor into RAGKO attenuated the weight loss and reduced TNF\u03b1 expression by RPMs. Co-culturing of erythroid cells suppressed TNF\u03b1 expression from RPMs in a phagocytosis-dependent manner. These findings implicate CD45 as a positive regulator of systemic inflammation and suggest erythroid progenitors are an anti-inflammatory agent in colitis.","language":"en"},{"key":"dc.language.iso","value":"eng","language":"en"},{"key":"dc.publisher","value":"University of British Columbia","language":"en"},{"key":"dc.rights","value":"Attribution-NonCommercial-NoDerivatives 4.0 International","language":"*"},{"key":"dc.rights.uri","value":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/","language":"*"},{"key":"dc.title","value":"The regulation of erythroid progenitors and T cells by CD45","language":"en"},{"key":"dc.type","value":"Text","language":"en"},{"key":"dc.degree.name","value":"Doctor of Philosophy - PhD","language":"en"},{"key":"dc.degree.discipline","value":"Microbiology and Immunology","language":"en"},{"key":"dc.degree.grantor","value":"University of British Columbia","language":"en"},{"key":"dc.date.graduation","value":"2020-05","language":"en"},{"key":"dc.type.text","value":"Thesis\/Dissertation","language":"en"},{"key":"dc.description.affiliation","value":"Science, Faculty of","language":"en"},{"key":"dc.description.affiliation","value":"Microbiology and Immunology, Department of","language":"en"},{"key":"dc.degree.campus","value":"UBCV","language":"en"},{"key":"dc.description.scholarlevel","value":"Graduate","language":"en"}]