investigator_user investigator user funding collaborators pending menu bell message arrow_up arrow_down filter layers globe marker add arrow close download edit facebook info linkedin minus plus save share search sort twitter remove user-plus user-minus
  • Project leads
  • Collaborators

MiRNA-155 regulates B cell function through its target PU.1

Elena Vigorito

0 Collaborator(s)

Funding source

Medical Research Council (MRC)
MiRNAs (miRNAs) are increasingly being recognised as major regulators of gene expression. Their expression provides an additional level of regulation beyond transcriptional control, permitting more rapid establishment of stable gene expression patterns. It is now apparent that miRNAs regulate many aspects of the immune system, including adaptive immune responses. During the course of adaptive immune responses B lymphocytes must respond rapidly to antigenic stimulation by initiating complex changes in gene expression that allow differentiation into effector and memory cells. These events lead to the production of high affinity antibodies and development of lasting immunological protection which underpins effective vaccination. The present work aims to test for a functional relation between a particular miRNA, miR-155, and one of its targets, PU.1. My previous work has implicated miR-155 for optimal adaptive immune responses of B cells in a cell-autonomous manner. I have shown that miR-155 is required for optimal immunoglobulin class switch recombination (CSR) and identified the transcription factor PU.1 as miR-155 direct target. In this project, I present some unpublished data establishing a causal relation of miR-155 and its target PU.1 for regulating CSR. I propose to follow up those observations by performing a thorough analysis of the significance of those observations in the context of adaptive immunity in vivo and to understand the molecular mechanisms by which miR-155 through its target PU.1 regulates the generation of switched B cells. The prospect of targeting miRNAs for therapeutic use is exciting and could open up new complementary treatments for cancer, inflammation or effective vaccination. There is already an antagonist for a miRNA in clinical trials for the treatment of hepatitis C. The proposed work will contribute to uncover the regulatory network regulated by miR-155 through its target PU.1 which may be exploited for effective vaccination.

Related projects