Leading the way to a cure


Inducing Tolerance in SLE through Modulation of Apoptotic Cell Receptors

Bhardwaj, Nina, MD, PhD

New York University School of Medicine

In systemic lupus erythematosus (SLE, or lupus), the immune system generates abnormal, autoreactive responses that target self antigens released by dying cells. There is an urgent need to develop approaches to prevent these processes or, at the very least, induce immune system tolerance for them. Tolerance is the process by which immune system cells are “taught” to recognize self from nonself proteins. Part of the problem with lupus is that immune system cells, particularly T and B cells, mistakenly view “self” proteins as foreign and develop anti-bodies against them or otherwise try to destroy them, leading to significant tissue damage. 

Dr. Bhardwaj’s team focuses on the role of dendritic cells, white blood cells that are often the first to identify pathogens and “present” them to T cells, which then develop an appropriate response. In their work, Dr. Bhardwaj’s team has found that dendritic cells can be manipulated to induce tolerance. 

With this grant, they plan to generate tolerogenic dendritic cells (TDC) that silence autoimmune T cells and block B cell antibody production. They found they can develop TDCs by aggregating certain receptors on the surfaces of dendritic cells. In healthy individuals, these receptors normally engage and then remove dying cells from the body (including those containing autoantigens) to prevent autoimmunity. Current studies are looking at which receptors exist on dendritic cells in people with lupus, and how similar are they to those from healthy people. The team will also explore novel ways to manipulate these receptors, including using pieces of dying cells to “turn off” dendritic cells.

What this study means for people with lupus: This study identifies a novel approach to halting the autoimmune process, one that could lead to the development of new therapies.

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