Mark Shlomchik, MD, PhD

Yale University, New Haven, CT

2011 Why the Lupus Immune System Reacts to Its Own DNA

In lupus, the patient’s immune system responds to his or her own body, targeting “nucleic acids” (DNA and RNA) essential to cell function. A key to solving lupus is to understanding why and how this response occurs.

(Scientists know that the response is made both by B cells, which produce “autoantibodies,” and by T cells, which not only help B cells make autoantibodies but also directly attack tissues like skin and vessels.)

Based on work by Dr. Shlomchik and many others it’s become clear how B cells are activated. But how T cells are activated remains a mystery. With LRI funding, Dr. Shlomchik will aim to fill this critical knowledge gap by engineering a new line of mice that illustrates how T cells that act against the body’s own tissues and organs (autoreactive T cells) are “turned on” in lupus.

To do this he will use T cells that recognize the classic lupus RNA-binding autoantigen “Sm”, which he recently isolated from lupus-prone mice. These cells will be used as a model to make mice in which all of the T cells can recognize this same lupus autoantigen.

This model can then be studied on normal and lupus-prone mice to help understand how T cells specific for a lupus antigen are kept from doing damage in a normal animal but cause disease in a lupus-prone mouse.