The regulation and function of Forkhead box O transcription factors FOXO1 and FOXO3 in T and iNKT lymphocytes
type: CreativeWork
description: T lymphocytes are critical components of an effective adaptive immune response, with different subsets performing proinflammatory and immuno-suppressive roles. In response to foreign antigens, naïve T cells activate expand and differentiate into effector T cells which mediate pathogen elimination. During the aftermath of pathogen clearance, a subset of effector T cells revert back to quiescence and differentiate into memory T cells. The Forkhead box O transcription factors FOXO1 and FOXO3 (to lesser extent) are essential for naïve and memory T cell differentiation. However, FOXO1 and FOXO3 function is not restricted to quiescent T cells; there is increasing evidence for a role in differentiation of effector T cells and in innate lymphocytes. The molecular mechanisms of how FOXO1 and FOXO3 control these functions is still poorly defined. In this thesis, we examine the relative expression of FOXO1 and FOXO3 in different lymphocyte populations and investigate exactly how FOXO1 and FOXO3 control lymphocyte functions. We use two novel knockin mouse lines developed by the Cantrell laboratory that contain LoxP flanked Foxo1-GFP and Foxo3-GFP reporter genes in the endogenous loci. This gave us the unique opportunity to accurately quantify and compare FOXO1 and FOXO3 expression and subcellular localisation in immune cells at a single cell resolution, as well as to functionally test the consequence of FOXO1 or FOXO3 deletion in T cells. Using the FOXO1-GFP and FOXO3-GFP knockin mice we quantified and compared FOXO1 and FOXO3 expression during T cell development and in peripheral T cells ex vivo. We show that the expression of FOXO1 increases with thymocyte development and is abundantly expressed in conventional naïve and effector T lymphocytes. Conversely, we found that FOXO3 is highly expressed in thymic progenitors and it is preferentially expressed in ‘innate’ like lymphocytes; invariant NKT (iNKT) cells and intraepithelial lymphocytes (IEL). Using the FOXO1-GFP knockin mo…
abstract: T lymphocytes are critical components of an effective adaptive immune response, with different subsets performing proinflammatory and immuno-suppressive roles. In response to foreign antigens, naïve T cells activate expand and differentiate into effector T cells which mediate pathogen elimination. During the aftermath of pathogen clearance, a subset of effector T cells revert back to quiescence and differentiate into memory T cells. The Forkhead box O transcription factors FOXO1 and FOXO3 (to lesser extent) are essential for naïve and memory T cell differentiation. However, FOXO1 and FOXO3 function is not restricted to quiescent T cells; there is increasing evidence for a role in differentiation of effector T cells and in innate lymphocytes. The molecular mechanisms of how FOXO1 and FOXO3 control these functions is still poorly defined. In this thesis, we examine the relative expression of FOXO1 and FOXO3 in different lymphocyte populations and investigate exactly how FOXO1 and FOXO3 control lymphocyte functions. We use two novel knockin mouse lines developed by the Cantrell laboratory that contain LoxP flanked Foxo1-GFP and Foxo3-GFP reporter genes in the endogenous loci. This gave us the unique opportunity to accurately quantify and compare FOXO1 and FOXO3 expression and subcellular localisation in immune cells at a single cell resolution, as well as to functionally test the consequence of FOXO1 or FOXO3 deletion in T cells. Using the FOXO1-GFP and FOXO3-GFP knockin mice we quantified and compared FOXO1 and FOXO3 expression during T cell development and in peripheral T cells ex vivo. We show that the expression of FOXO1 increases with thymocyte development and is abundantly expressed in conventional naïve and effector T lymphocytes. Conversely, we found that FOXO3 is highly expressed in thymic progenitors and it is preferentially expressed in ‘innate’ like lymphocytes; invariant NKT (iNKT) cells and intraepithelial lymphocytes (IEL). Using the FOXO1-GFP knockin mo…
author: Nomura, Aneela
language: eng
date published: 2019
date modified: 2026-07-24T02:08:46Z
provider: University of Dundee
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Dundee