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[Comment] The extending scope of kinase inhibition in immune diseases

Functional mutation analyses in patients with immune deficiencies identified Janus kinases (JAKs) as plausible regulators of the immune response. Thereafter, elegant signalling biology generated a compelling rationale for the use of small molecule inhibitors to recapitulate the cytokine blocking activities of biologics. JAK inhibitors have thus emerged as novel immune modifiers that target cytokines via blockade of intracellular cytokine receptor signalling pathways. Four members of the family (JAK1, JAK2, JAK3, and TYK2) can form a variety of heterodimers (eg, JAK1/JAK2 and JAK1/JAK3) and transmit signals from the cell membrane to the nucleus (via cytosolic shuttling proteins) to activate leucocytes and stromal cells and drive inflammation.