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Janus kinases (JAK) are key molecules required for over 50 cytokines and growth factors that signal through type 1 and type 2 cytokine receptors and phosphorylate several substrates including Signal Transducers and Activation of Transcription (STAT) factors. The JAK/STAT signaling is essential for the ...

Janus kinases (JAK) are key molecules required for over 50 cytokines and growth factors that signal through type 1 and type 2 cytokine receptors and phosphorylate several substrates including Signal Transducers and Activation of Transcription (STAT) factors. The JAK/STAT signaling is essential for the development, differentiation, and function of immune cells and for human immune response to environmental cues. In the past decade, the development of JAK inhibitors has led to the approval of multiple compounds for the treatment of a wide variety of autoimmune and inflammatory diseases in rheumatology, dermatology, and gastroenterology. Further indications, still under investigation, will likely expand the landscape of JAK inhibition to other immune-mediated inflammatory diseases. These JAK inhibitors have also been valuable tools to further characterize the role of cytokines in biological and immune processes and, importantly, to also further our understanding of their role in pathological conditions.

This Research Topic aims to provide an overview of the progress made in the field of JAK inhibition and JAK/STAT agonism (cytokine-based modalities) for the treatment of autoimmune and inflammatory diseases.
The role of JAK isoforms pairing in type 1 and type 2 cytokine receptors signaling has been well characterized but the relative contribution of each one of the two JAK isoforms to the signaling output of various cytokine receptors is poorly understood. In this regard, a better understanding of JAK isoform selective inhibition and the relative clinical consequences will be an important aspect to optimize their clinical utility.

We seek Original Research, Review, Perspective and Clinical Trial manuscripts that cover, but are not limited to, the following aspects of the mechanistic and therapeutic effects of inhibiting JAK/STAT signaling or modulate a specific cytokine receptor with a therapeutic agent:

• Mechanistic studies of JAK inhibition
• New clinical characterization of JAK inhibitors
• New technologies and/or biomarkers that could be utilized to optimize the use of JAK inhibitors or predict their efficacy
• Novel approaches to modulate cytokine receptor signaling




Dr. Jean-Baptiste Telliez is an employee of Pfizer Inc, investigating JAK inhibition therapeutics. Dr. Olli Silvennoinen is co-founder of Ajax therapeutics, involved in the development of JAK inhibitors for cancer therapy.

Keywords: Cytokines, JAK, Autoimmunity, Inflammation, Kinase Inhibitors, molecular regulation of JAK kinases, structure of JAK kinases, JAK inhibitors


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