IL-2Rα Inhibitors

Interleukin-2 receptor alpha (IL-2Rα) is a crucial component of the IL-2 receptor complex that plays a central role in regulating immune responses. IL-2Rα is primarily expressed on the surface of activated T cells, where it binds to IL-2, a cytokine that is pivotal for T cell proliferation and function. Upon IL-2 binding, IL-2Rα triggers a signaling cascade that activates downstream pathways, including the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. This activation promotes T cell growth, survival, and differentiation. IL-2Rα signaling is intricately involved in immune homeostasis, immune responses to infections, and the regulation of autoimmunity.

IL-2Rα inhibitors are compounds that modulate the IL-2Rα-mediated signaling pathway. These inhibitors can have both direct and indirect effects. Direct inhibitors specifically target the IL-2Rα receptor itself or its downstream signaling components. Monoclonal antibodies like daclizumab and basiliximab directly target IL-2Rα, reducing its availability for binding IL-2 and dampening T cell activation. Indirect inhibitors encompass a broader range of compounds that affect IL-2Rα signaling by targeting pathways or molecules linked to its activation. Janus kinase inhibitors, such as tofacitinib and baricitinib, intervene at the JAK-STAT pathway level, hindering downstream signaling events and attenuating immune responses. Calcineurin inhibitors, such as cyclosporine and tacrolimus, inhibit T cell activation, including IL-2Rα-mediated activation, by blocking the action of key enzymes in the immune signaling cascade.