2015 ACR/ARHP Annual Meeting: Role of Tumor Necrosis Factor Cytokines in Autoimmune Diseases Examined

For patients with autoimmune disease, the research to date shows that the TNF-family cytokine TL1A and its receptor DR3 may be pathogenic.
Image Credit: Alexander Raths/shutterstock.com

SAN FRANCISCO—To date, evidence on the efficacy of blocking the cytokine tumor necrosis factor (TNF) and its receptors in autoimmune diseases has resulted in the approval by the Food and Drug Administration (FDA) of five anti-TNF agents. Less well known, according to Richard Siegel, MD, PhD, chief, Immunoregulation Section, Autoimmunity Branch, and Clinical Director, NIAMS, National Institutes of Health, Bethesda, Md., are 17 other cytokines genetically and structurally related to TNF that comprise the TNF superfamily and play a significant role in autoimmune diseases. Each of these cytokines, along with each cytokine receptor, play a different role in disease activation, and ongoing research is looking at how these cytokines work alone or in combination in the pathogenesis of autoimmune diseases to further uncover potential therapeutic targets.

In the session, Tumor Necrosis Factor (TNF) and Beyond: The TNF-Tumor Necrosis Factor Receptor Cytokine Superfamily From Bench to Bedside, at the 2015 ACR/ARHP Annual Meeting, a panel of experts talked about the biology and therapeutic relevance of the tumor necrosis factor receptor (TNFR) family ligands and receptors to rheumatology. Among the talks were presentations on specific cytokines, TL1A and OX40L, and evidence on their role in pathogenesis of autoimmune diseases and early data on potential targets for therapy.

Cytokine TL1A & Receptor DR3

Dr. Siegel opened the session by describing the current research on TL1A and its receptor, DR3.

Dr. Siegel

Past research has shown that TNF cytokines share very specific functions and that many mutations linked to these shared functions are linked to diseases. Importantly, he said that 32 of 98 genes encoding these shared functions of TNF cytokines (TNFSF) and their receptors (TNFSRSF) are associated with at least one autoimmune disease.

Thus, blockade of TNF cytokine signaling may provide a successful therapeutic strategy.

Toward that ultimate goal, he talked about current and ongoing research on the specific cytokine, TL1A, also known as TNFSF15.¹ For patients with autoimmune disease and, particularly those with rheumatic disease, he said the research to date shows that the TNF-family cytokine TL1A and its receptor DR3 may be pathogenic.

From mouse models, the research shows that TL1A is a co-stimulator of lymphocyte activation and is essential for the development of mouse models of various autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and asthma, he said.