Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2017.23 Figure 1 Overview of JAK–STAT signalling in host defense and cellular homeostasis Figure 1 | Overview of JAK–STAT signalling in host defense and cellular homeostasis. Type I and II cytokines bind their receptors with subsequent intracellular signalling via the Janus kinase and signal transducer and activator of transcription (JAK–STAT) pathway. The cytoplasmic domain of cytokine receptors associates with various JAKs (JAK1, JAK 2, JAK 3 and non-receptor tyrosine-protein kinase 2 (TYK2)). These kinases act via autophosphorylation as well as STAT phosphorylation. Key host inflammatory responses are mediated through these interactions, including those that lead to autoimmune inflammatory diseases such as rheumatoid arthritis. Shown here are the signalling pathways of a select group of cytokines, as well as cytokine receptor dimerization and their association with JAKs. Of note, the figure depicts important interactions in the host defense against infection including the signalling of both type I interferons and interferon-γ (IFNγ). Type I interferons signal via type II cytokine receptors associated with JAK1 and TYK2, whereas IFNγ signals via type II cytokine receptors associated with JAK1 and JAK2. These signalling pathways are particularly important to host antiviral responses. Other signalling pathways mediated by JAK–STAT are important for cellular homeostasis, including lymphocyte production and erythropoeisis. GM-CSF, granulocyte-macrophage colony-stimulating factor. Winthrop, K. L. (2017) The emerging safety profile of JAK inhibitors in rheumatic disease Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2017.23