Translational Positioning of Janus Kinase (JAK) Inhibitors in Alopecia Areata

نویسندگان

  • Ulrike Blume-Peytavi
  • Annika Vogt
چکیده

Alopecia areata (AA) is an autoimmune disease due to T cell attack of observation made in a special patient is complemented with mechanisthe hair follicles and breakdown of their immune privilege resulting in transient non-scarring hair loss which may last from weeks to decades and which presents an enormous psychological burden. As so far no FDA approved successful treatments for AA are available, new hope and light arose on the horizon with the recently published genome wide association studies in AA patients revealing new molecular pathways disrupted in AA including autophagy/apoptosis, transforming growth factor beta/Tregs and JAK (Janus family of non-receptor protein tyrosine kinase) signaling (Petukhova et al., 2010; Betz et al., 2015). Thus, today it is assumed that CD8 + NKG2D+ T effector memory cells mediate alopecia areata in part through Janus kinase (JAK) signaling and that alopecia areata might be treated with JAK inhibitors. This assumption has been supported by clinical use of JAK inhibitors within a clinical study setting (Xing et al., 2014) or observed as a “side effect”, when JAK inhibitor treatment of another underlying disease resulted in regrowth of longstanding patchy or universal alopecia areata (Craiglow and King, 2014; Pieri et al, 2015). Xing et al., 2014 demonstrated that the interferon-γ (IFNγ)-signaling pathway is upregulated in AA-lesional skin, and that the use of JAK inhibitorswas able to reverse symptoms of the disorder in mice and in three humans with AA. While different groups (Craiglow and King, 2014; Pieri et al, 2015; Higgins et al, 2015) reported successful use of ruxolitinib, a JAK1/2 inhibitor licensed for treating myelofibrosis, others reported successful use of the JAK 1/3 inhibitor tofacitinib in AA while using it for treating psoriasis (Craiglow and King, 2014). In this issue of EBioMedicine, Jabbari et al. followeduponhair growth observed in a patient under baricitinib therapy, also a JAK1/2 inhibitor and studied JAK inhibitor action in the C3H/HeJ graft-recipient mouse model of AA (Jabbari et al., 2015). Under JAK inhibitor treatment, CD8+ cell infiltrates and MHC class I and II expressions were markedly reduced in C3H/HeJmice graftedwith alopecic skin, both in a preventive and a therapeutic setting. In addition, gene expression profiling using the Alopecia Areata Disease Activity Index (ALADIN) biomarker for response to treatment confirmed the assumed normalization of the IFNgamma gene expression signature. The approach of Jabbari et al. represents an excellentmodel for translational work, where a specific clinical

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عنوان ژورنال:

دوره 2  شماره 

صفحات  -

تاریخ انتشار 2015