Dr. Schroeder on the Importance of JAK Inhibition in GVHD

Mark A. Schroeder, MD, an associate professor at the Washington University School of Medicine in St. Louis, discusses the importance of JAK inhibition in graft-versus-host disease (GVHD).

New therapies are emerging for patients with acute GVHD, such as JAK inhibitors, α-1 antitrypsin, and a novel agonist antibody called IL-22. JAK inhibition works by blocking cytokines, which are essential for stimulating GVHD response. JAK-STAT signaling is critical for immune cell development, says Schroeder. By blocking this signaling pathway with a JAK inhibitor, such as ruxolitinib (Jakafi) or itacitinib, you can block these essential signals, which are critical for T-cell proliferation.

A critical cytokine called interferon-gamma signals through JAK1/2. JAK1/2 inhibition prevents T cells from reaching the organs that are involved with GVHD, such as the gut, and other sites of GVHD, says Schroeder. Blocking interferon gamma or other cytokines decreases the inflammatory milieu of GVHD and effects the presentation of antigens in the stimulation of T cell response. Recently, other groups have shown that blocking interferon-gamma signaling, specifically in the gut, decreases damage to essential cells that regenerate the gut, concludes Schroeder.