IFN-γ enhances cell-mediated cytotoxicity against keratinocytes via JAK2/STAT1 in lichen planus

Authors: Shuai Shao, Lam C. Tsoi, Mrinal K. Sarkar, Xianying Xing, Ke Xue, Ranjitha Uppala, Céline C. Berthier, Chang Zeng, Matthew T. Patrick, Allison C. Billi, Joseph Fullmer, Maria A. Beamer, Bethany E. Perez White, Spiro Getsios, Andrew Schuler, John J. Voorhees, Sung Won Choi, Paul W. Harms, J. Michelle Kahlenberg, Jóhann E. Guðjónsson - Science Translational Medicine 2019 cited by 178

T cell-mediated cytotoxic responses through MHC class I induction in a coculture model. We show that this process is dependent on Janus kinase 2 (JAK2) and signal transducer and activator of transcription 1 (STAT1), but not JAK1 or STAT2 signaling. Last, using drug prediction algorithms, we identify JAK inhibitors as promising therapeutic agents in LP and demonstrate that the JAK1/2 inhibitor baricitinib fully protects keratinocytes against cell-mediated cytotoxic responses in vitro. In summary, this work elucidates the role and mechanisms of IFN-γ in LP pathogenesis and provides evidence for the therapeutic use of JAK inhibitors to limit cell-mediated cytotoxicity in patients with LP.