Tyrosine kinase 2 (TYK2) is an intracellular protein belonging to the Janus kinase (JAK) family of enzymes. These proteins transmit signals from the cell’s exterior to its interior. TYK2 is involved in various cellular communication processes, fundamentally influencing how cells respond to external cues, especially those related to immune function.
The Role of TYK2 in the Body
TYK2, a Janus kinase (JAK) family enzyme, relays immune signals within cells. These kinases transmit signals initiated by cytokines, which are protein messengers in the immune system. TYK2, along with other JAK proteins like JAK1, JAK2, and JAK3, forms pairs to facilitate this signal relay.
TYK2 is involved in pathways with cytokines such as interleukin-12 (IL-12), interleukin-23 (IL-23), and Type I interferons (IFN). When these cytokines bind to cell surface receptors, TYK2 activates and passes the signal to the cell’s nucleus. This activates transcription factors, like STAT proteins, which regulate gene expression and influence immune responses and inflammation. This allows the immune system to respond to various stimuli.
TYK2 and Autoimmune Conditions
Dysregulation or overactivity of TYK2 contributes to chronic inflammation, a hallmark of many autoimmune diseases. In these conditions, the immune system mistakenly targets and attacks its own tissues. Aberrant signaling through TYK2 pathways can perpetuate this harmful immune response.
TYK2 is involved in several autoimmune conditions. These include psoriasis, a skin disorder with inflamed, scaly patches, and psoriatic arthritis, which affects the joints. TYK2 dysregulation is also implicated in systemic lupus erythematosus (SLE), a condition affecting multiple organs, and inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. Genetic variations in the TYK2 gene can also influence the risk of developing various autoimmune diseases.
Targeting TYK2 in Medicine
Understanding TYK2’s role led to the development of TYK2 inhibitors. These drugs selectively block TYK2 enzyme activity, dampening excessive immune responses and reducing inflammation in autoimmune conditions. Unlike broader immunosuppressive drugs, TYK2 inhibitors offer a more targeted approach by interfering with TYK2-mediated signaling pathways.
These therapies interrupt the communication of pro-inflammatory cytokines like IL-12, IL-23, and Type I IFNs, often overactive in autoimmune diseases. By inhibiting TYK2, these medications reduce inflammatory mediators and mitigate immune responses contributing to disease symptoms. Some TYK2 inhibitors bind to a regulatory part of the enzyme, rather than its active site, which contributes to their specificity and reduces off-target effects.