Breakthrough in understanding human immune response has potential for the development of new drug therapies

July 6, 2012

(Medical Xpress) -- A team of researchers at Trinity College Dublin’s School of Medicine has gained new insights into a protein in the human immune system that plays a key role in the protective response to infection and inflammation. The research findings have just been published in the internationally renowned peer-reviewed Journal of Biological Chemistry.

The TCD researchers investigated whether signalling via a protein known as the ‘LFA-1 integrin’ influences gene expression in immune cells called ‘T-cells’.  In doing so, they discovered what is called “ a genetic signature”, that is a group of genes responding to the signal that make T-cells fail to respond to a controlling molecule called  transforming growth factor-β (TGF-β).

“This is a bit like removing the handbrake and setting the immune system into action,” says Professor of Medicine, Dermot Kelleher who led the research.

The research may also have implications for treating inflammatory diseases where drugs targeting LFA-1 have had unacceptable and serious side effects such as progressive multi-focal leukoencephalopathy (PML) in the brain. “If we more fully understand the signalling mechanism leading to downstream gene regulation by LFA-1, we may be able to devise selective therapies to better treat various autoimmune diseases without major side effects such as PML,” according to Professor Kelleher.

Scientists have known for decades that LFA-1 is responsible for the majority of T-cell migratory behaviours associated with the . Central to the success of immune responses that restrain inflammation are regulatory molecules, including a multifunctional cytokine TGF-β, which is essential for the development and function of an immune cell type, called the regulatory T-cells. In the current study, Trinity College Dublin scientists conducted a genome wide analysis and detected that the expression of several genes were altered when T-cells were triggered to migrate to a site of inflammation through the interaction of LFA-1 with another protein called ICAM-1. This research was performed in collaboration with the Immunology Research Group at the National Children’s Research Centre at Our Lady’s Children’s Hospital, Crumlin led by SFI Stokes Professor of Translational Immunology, Padraic Fallon.

“There is still much to learn about the genetic changes induced by the LFA-1 signal, but our studies are the first to show that a regulatory T-cells associated signal is influenced,” says TCD research fellow in clinical medicine, Dr. Navin Kumar Verma, a lead author on the study. “The findings are novel and significantly contribute to the understanding of how the organism mounts an immune response. Several other genes identified here offer a general framework for future research in order to identify excellent targets for novel therapies for immune-mediated human diseases such as rheumatoid arthritis or inflammatory bowel disease.”

Explore further: A major step forward in fighting superbugs

More information: The full citation of the paper is: Verma NK, Dempsey E, Long A, Davies A, Barry SP, Fallon PG, Volkov Y, and Kelleher D (2012) Leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction induces a novel genetic signature resulting in T-cells refractory to transforming growth factor-β signalling. Journal of Biological Chemistry. www.jbc.org/content/early/2012 … 6/15/jbc.M112.376616

Related Stories

A major step forward in fighting superbugs

July 29, 2011
New research has identified a novel mechanism by which humans can defend themselves against the well known hospital superbug, Clostridium difficile.  The study provides us with critical information for the development ...

A central regulator of the inflammatory response shows signs as a target for therapies against autoimmune disease

March 30, 2012
Some bacterial infections trigger the formation of structures known as granulomas, which essentially quarantine compromised cells. “Infected macrophages get surrounded by other immune cells, such as T cells and neutrophils,” ...

Study shows how immune cells rally defenses against infection while keeping harmful inflammatory reactions in check

May 11, 2012
T cells represent a significant component of the ‘muscle’ in the immune system, promoting aggressive action against perceived threats or restraining fellow immune cells from launching an unhealthy autoimmune response ...

The case of the missing monocyte: Scientists investigate gene that appears to protect against rheumatoid arthritis

October 11, 2011
(Medical Xpress) -- An estimated 1.3 million people in the United States suffer from rheumatoid arthritis. The causes behind this chronic disease — which can exhibit itself as pain, swelling, stiffness, deformation, ...

Recommended for you

Breast milk found to protect against food allergy

November 20, 2017
Eating allergenic foods during pregnancy can protect your child from food allergies, especially if you breastfeed, suggests new research from Boston Children's Hospital. The study, published online today in the Journal of ...

How a poorly explored immune cell may impact cancer immunity and immunotherapy

November 17, 2017
The immune cells that are trained to fight off the body's invaders can become defective. It's what allows cancer to develop. So most research has targeted these co-called effector T-cells.

Asthma attacks reduced in tree-lined urban neighborhoods

November 17, 2017
People living in polluted urban areas are far less likely to be admitted to hospital with asthma when there are lots of trees in their neighbourhood, a study by the University of Exeter's medical school has found.

How the immune system identifies invading bacteria

November 16, 2017
The body's homeland security unit is more thorough than any airport checkpoint. For the first time, scientists have witnessed a mouse immune system protein frisking a snippet of an invading bacterium. The inspection is far ...

Can asthma be controlled with a vitamin supplement?

November 16, 2017
The shortness of breath experienced by the nearly 26 million Americans who suffer from asthma is usually the result of inflammation of the airways. People with asthma typically use albuterol for acute attacks and inhaled ...

Newly found immune defence could pave way to treat allergies

November 16, 2017
Scientists have made a fundamental discovery about how our body's immune system clears harmful infections.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.