Regulatory T cells (Tregs) and their function in T1D

Dr. Anne Maria Pesenacker, a JDRF-funded investigator at the University of British Columbia and now at UCL’s Institute of Immunity and Transplantation, is examining how regulatory T cells (Tregs) function in health and how best to monitor their fitness.

Tregs are a specialized type of white blood cell that prevent immune cells from attacking the body. When they stop functioning, autoimmune diseases such as type 1 diabetes (T1D) can occur. In T1D, Tregs fail and effector T cells attack and destroy the insulin-producing beta cells in the pancreas resulting in a loss of blood sugar control, as well as a lifelong dependence on insulin injections.

Dr. Pesenacker’s initial research used a test to observe Treg health in ustekinumab (a manufactured human antibody against naturally occurring proteins that affect the immune system and immune-mediated inflammatory disorders) therapy. She performed Treg gene signature measures on the samples collected from the ustekinumab phase I/II trial and developed an algorithm to predict which patients had a rapid versus a slow decline in response to treatment. More recently, she optimized a way of employing a gene modification technology called CRISPR for the engineering of primary human cells in order to study the function of specific integral proteins involved in cell signalling in health and T1D.

The development of this Treg gene signature marks a major achievement in research and could be a step towards a robust biomarker of immune status in T1D. Testing this biomarker across multiple future clinical studies may also lead to the advancement of universal algorithms that could be applied to identify rapid vs slow decliners, monitor T1D over time, and/or select individuals likely to respond to immunotherapy.

One of two promising researchers to receive an Eli Lilly Canada post-doctoral fellowship grant from the JDRF Canadian Clinical Trial Network (JDRF CCTN) in 2017, Dr. Pesenacker has learned how to establish and run translational immunology studies under the mentorship of Dr. Megan Levings and by working closely with key clinical trial personnel at BC Diabetes, the Immune Tolerance Network and the CCTN. In 2018, Dr. Pesenacker was awarded a career development fellowship from Versus Arthritis and moved to the UCL Institute of Immunity and Transplantation (London, UK) to expand her research, develop her independent research programme and become well-versed in translating research findings into clinical trials.

JDRF is proud to support a talented young investigator like Dr. Pesenacker.

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