JAK-STAT Inhibition in Atopic Dermatitis

JAK-STAT Inhibition in Atopic Dermatitis Posted By:
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More than 21 million people in the US are affected by atopic dermatitis (AD). This chronic, immune-mediated disease is a key focus for pharmaceutical research and development. Recently, the FDA approved 2 oral Janus kinase (JAK) inhibitors (upadacitinib and abrocitinib) for AD. JAK inhibitors have been used successfully in other disease states, but have only recently been introduced in the treatment of AD.

The JAKs—composed of JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2)—are a group of molecules that are integral in the JAK-signal transducer and activator of transcription (STAT) signaling pathway—an intracellular pathway that regulates inflammatory cytokines and plays a critical role in the pathogenesis of various dermatologic diseases.

When a cytokine binds to its respective extracellular receptor, the JAK-STAT signaling cascade is activated. This binding catalyzes JAK phosphorylation. STAT proteins are then translocated into the cell nucleus, where the STAT proteins regulate gene expression—specifically those that are responsible for cytokine synthesis as well as synthesis of other mediators that act on various cell types, including immune cells and skin cells. JAK inhibitors are unique in that they work to impede activation of the JAK-STAT signaling pathway.

By inhibiting the JAK-STAT pathway, JAK inhibitors limit cytokine production and reduce atopic symptoms such as itch and inflammation. It will be exciting to see not only the impact of these medications on the vast population suffering from AD, but also the future developments in understanding and modifying the JAK-STAT pathway.

References
  • Guttman Krader C. JAK-STAT inhibition an attractive target for atopic dermatitis drugs. Dermatology Times. 2020;41:26.
  • National Eczema Association. New prescription treatments. nationaleczema.org/new-treatments/. Accessed Feb 8, 2022.

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Filed under: Dermatology

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