The Role of Transcription Factor Krüppel-like Factor 2 in Lymphocyte Migration and Homeostasis

Abstract

The immune system is charged with the task of protecting the body from pathogens and clearing apoptotic or cancerous cells to prevent chronic disease. Controlled cell migration shapes lymphocyte subset development, homeostasis, and immune responses in a lineage specific manner. Although frequently associated with lymphocyte survival and quiescence, one of the primary functions of the transcription factor Krüppel-like factor 2 (KLF2) is to direct lymphocyte migration. In this thesis I report that KLF2 differentially regulates CD4+CD25- and CD8+ T cell migration, and is necessary for natural killer (NK) cell homeostasis. Surprisingly, in CD4+CD25- and CD8+ T cell lineages, KLF2-directed migration patterns are dispensable for effector function but may promote peripheral tolerance. NK cells have been long thought to promote viral clearance and tumor surveillance. In the NK cell compartment KLF2 controls homeostasis by (a) suppressing immature NK cell proliferation and (b) promoting localization toward IL-15 rich niches necessary for mature NK cell differentiation and survival. Through these novel KLF2-directed mechanisms it may be possible to increase the number and persistence of mature NK cells to improve NK cell based cancer therapies.