Leading the way to a cure

Lupus Research Update: 2012 Volume 3

Volume 3, 2012 - Online Edition | In This Issue

Looking at T Cell Function to Better Understand Lupus >
Back to Basics — T Cells... B Cells... And Lupus >
Researching B Cells Reveals Clues About Lupus >
Faces of Lupus: Sisterly Love in Michigan Benefits Everyone with Lupus >
Genetic Gateways to Understanding Lupus - New ALR Grant Awardees >
Lupus News Corner >

Looking at T Cell Function to Better Understand Lupus

The function of T cells intrigues renowned scientists like Alessandra Pernis, MD— and with good reason. T cells are a key component of the body’s immune system and its ability to attack antigens or foreign invaders — such as bacteria, viruses, chemicals, and even pollens.

Warding off antigens is the primary job of a T cell and one of the major ways it achieves this is by releasing chemicals. When a T cell recognizes an antigen, it will produce chemicals known as ctyokines that cause B cells to multiply and release immune proteins called antibodies.

With assistance from three ALR grants, Dr. Pernis has been searching for clues to discover why T cells become overactive and what causes the body to be unable to differentiate between antigens and healthy tissue in lupus patients.

Dr. Pernis has discovered that the absence of the IRF4 molecule leads to malfunction of T cells and B cells. “It’s a critical factor for the activation of these cells,” Dr. Pernis reveals. “It is a question of balance, when you don’t have IRF4, your immune system is severely impaired... when you have too much you can get disease.”

IRF4 is a central player in the immune response, and Dr. Pernis believes that two molecules, DEF-6 and SWAP-70, control its function: “Like your car, you don’t want to accelerate out of control, you just want to make sure you go the right speed. That’s basically what these molecules are doing — making sure that IRF4 doesn’t get out of control.”

Building on the knowledge she has gained in studying T cells for more than 10 years, Dr. Pernis — with her latest ALR grant — is now focusing on Tregs, T regulatory cells, a component of the immune system that suppresses immune responses to other cells.

In an effort to make the process easier to understand, Dr. Pernis explains: “In lupus, T helper cells are in a sense the ‘bad guys’ because they drive autoimmunity, and Tregs are the ‘good guys’ because they block T helper cells. By grasping a better understanding of Tregs and T helper cells, we hope to reveal why some people have mild symptoms of the disease, while others experience more severe manifestations.”

The ALR is proud to fund such cutting-edge lupus investigations, and Dr. Pernis — an ALR donor herself — is grateful to the organization for allowing her to execute her groundbreaking work with T cells.

“The ALR has done incredible work, giving scientists like me an amazing roadmap,” she said. “With ALR funding, geneticists discovered different variants that are implicated in lupus. This tremendous work enables those of us who are investigating more basic mechanisms to focus on those molecules. Our aim is to understand exactly how deregulations — like those in T cells — contribute to lupus.”