Role of JAKs in myeloid cells and autoimmune diseases

Abstract

＊ ＊ ＊ ＊ In the treatment of autoimmune diseases, therapy targeting inflammatory cytokines such as tumor necrosis factor and interleukin -6 has shown dramatic effect. In addition to these biological agents, several small molecules are currently in clinical development for the treatment of autoimmune diseases. Due to the important role of Janus kinase (JAK) in multiple cytokine signaling pathways, JAKs are essential not only for the development of the immune system but also in inflammatory responses and in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA). Tofacitinib, a novel selective JAK inhibitor, has shown high efficacy in clinical trials for RA and is known to be selective against JAK1 and JAK3. In addition to its therapeutic potential, tofacitinib is a favorable reagent to study the roles of JAKs in vivo. Dendritic cells are antigen-presenting cells that regulate T-cell responses and have been implicated in RA pathogenesis. Meanwhile, macrophages are resident phagocytic cells in lymphoid and non-lymphoid tissues and are believed to be involved in steady-state tissue homeostasis via the clearance of apoptotic cells and the production of growth factors. Macrophages also play an important role in synovial inflammation and tissue destruction in RA. Although the biological roles of JAKs in lymphocytes are well known, its function in monocyte-lineage cells remains elusive. This review describes the role of JAKs in myeloid cells and autoimmune disease.