Affecting the effectors. JAK inhibitors modulation of immune cell numbers and functions in patients with rheumatoid arthritis

Introduction The Janus kinase family includes four members - JAK1, JAK2, JAK3, TYK2 - that are selectively associated with type I and II cytokine receptors. Jak-inhibitors (Jakinibs) are a new class of drugs for treating inflammatory diseases. Five Jakinibs are currently available for Rheumatoid Arthritis (RA): tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib. Considering the role of cytokines and growth factors in immune cell survival and activation, the anti-proliferative and suppressive effects of Jakinibs on these cells are predictable. Areas covered This review summarizes Jakinibs' effects on immune populations in vitro and in vivo. In vitro, Jakinibs affected T and B lymphocytes, monocytes, neutrophils and dendritic cell proliferation. T helper, B cell differentiation, and cytokine secretion . Accordingly, changes in the number of lymphocytes, natural killer (NK) cells, and neutrophils have been reported during the randomized clinical trials with all the Jakinibs, reverting after drug withdrawal. Expert opinion In vitro and in vivo studies showed that the numbers and the function of immune cells are influenced by Jakinibs. Nonetheless, their effects do not seem to represent a major safety issue as these changes do not correlate with the onset of serious infection despite the increased rates of herpes zoster reactivation.