Dr. Lauren Henderson – Autoreactivity of Regulatory T cells in oligo JIA

Dr. Lauren Henderson – Autoreactivity of Regulatory T cells in oligo JIA

Dr. Lauren Henderson received a BA from Cornell University with majors in neurobiology and psychology. She was first exposed to the importance of clinical research through Postbaccalaureate Intramural Research and Training Program at the National Institutes of Health. After a year at NIH, she moved on to Harvard Medical School. She completed a pediatric internship and residency at Boston Children’s Hospital followed by a fellowship in pediatric rheumatology at Boston Children’s Hospital. Currently, Dr. Henderson is an Assistant Professor at Harvard Medical School and an attending pediatric rheumatologist at Boston Children’s Hospital.

Arthritis Through the Ages

Juvenile Idiopathic Arthritis (JIA) is the most common form of arthritis in patients under sixteen years of age. Depending on severity, it can cause persistent joint pain, swelling and stiffness. Some children may experience symptoms for only a few months, while others have symptoms for many years. Certain types of JIA can lead to serious complications like growth problems, joint damage, and eye inflammation. Treatment focuses on controlling pain and inflammation, improving function, and preventing damage. Oligoarticular juvenile idiopathic arthritis (oligo JIA) is defined as JIA involving fewer than five joints. It is the most common subgroup, constituting approximately 50 percent of cases of JIA. The disease’s exact cause is not fully understood, but it is often attributed to a combination of genetic and environmental factors.

Not Lost in Translation

Translational research is a term often used interchangeably with translational medicine, translational science or bench to bedside. It refers to the effort to build on basic scientific research to create new therapies, medical procedures, or diagnostics. Basic biomedical research is based on studies of disease processes using, for example, cell cultures or animal models. The basic findings in a laboratory setting are then carried over (translated) into potential treatments for disease. This particular approach can be extremely effective as physician and researcher are one and the same, giving them a unique perspective and real-life experience of the potential impact of their research.

In addition to caring for children with complex autoimmune conditions, Dr. Henderson conducts translational research regarding the loss of immunologic tolerance in pediatric rheumatologic disorders like JIA.  Immune tolerance refers to our bodies ability to identify cells which are our own and therefore tolerate them so that an immune response is not launched. In autoimmune conditions the body doesn’t appropriately distinguish between self and non-self and an immune response is elicited by our own cells leading to excessive inflammation.

Calling in the Cavalry

Dr. Henderson will be using her ANRF grant to investigate the ability of regulatory T cells to control inflammation in oligoarticular juvenile idiopathic arthritis. Regulatory T cells are a subpopulation of T cells with key roles in immune modulation, in particular maintaining tolerance to self-antigens and preventing autoimmune condition. This is achieved by suppressing or down regulating induction and proliferation of other types of T cells known as effector T cells, which actively respond to a stimulus such as a virus or foreign bacterial cell (bearing in mind that if something is determined as foreign a certain level of inflammation is normal and required to fight the infection). Basically, regulatory T cells are similar to army scouts, they determine whether something represents a threat and whether the soldiers (effector T cells) should be called in.

Synovial fluid is a viscous fluid (the viscosity can change when under force), similar in consistency to raw egg white, functions to reduce friction in articular cartilage in joints during movement. Samples of blood and synovial fluid from oligo JIA patients will be examined by Dr. Henderson in order to evaluate the ability of regulatory T cells to control inflammation in this disease. Are the scouts calling in the cavalry when necessary (when foreign bodies are present) or are they eliciting friendly fire against self-cells? Through previous research Dr. Henderson has already identified regulatory T cells in the synovial fluid which express inflammatory cytokines thus leading to increased inflammation. In addition, she will be collaborating with Dr. Stephen Elledge who has developed the breakthrough technology, TScan, that allows for the rapid and unbiased discovery of the physiologic targets of any T cell.

Yes, we (s)Can

“TScan is dedicated to creating life-changing T cell therapies for patients by unleashing the untapped potential of the human immune system.” TScan uses a proprietary genome-wide, high-throughput target identification screen, designed to rapidly identify the natural targets of T cell receptors.

With TScan, T cells are engineered to express a T cell receptor (TCR) of interest. These are then mixed with a genome-wide library of target cells, each of which expresses a different protein fragment. In each target cell, the protein fragment is processed by the proteasome (protein complexes which degrade unneeded or damaged proteins by proteolysis) and the resulting peptides are displayed naturally on cell-surface of major histocompatibility complex (MHC) proteins. MHC is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. If a T cell recognizes the peptide-MHC complex on a target cell, it attempts to kill the target cell, thereby activating a fluorescent reporter in the target cell. By sorting for fluorescent target cells and sequencing their expression cassettes, the natural target(s) of the T cell are revealed.

Using this technology, Dr. Henderson aims to evaluate the autoreactivity of regulatory T cells in oligo JIA. The overall goal being to better understand the mechanisms of oligo JIA and identify novel treatment approaches.

“As a pediatric rheumatologist, I care for a large number of children with JIA. I would like to better understand JIA so I can take better care of my patients. It is important to discover what pathways are driving this disease so new treatments can be developed. Further, identifying biomarkers could help the physician decide what treatments are best for each patient.  It is only through studying samples from children with this disease can we make progress and improve outcomes for patients.”


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Article Author
Arthritis National Research Foundation
arthritisresearch@curearthritis.org

The Arthritis National Research Foundation's mission is to provide initial research funding to brilliant, investigative scientists with new ideas to cure arthritis and related autoimmune diseases. Writing articles about the patients affected and the science being done to find a cure shows why we need to come together to #CureArthritis!

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