TYK2 signaling as a molecular bridge between cytokine storm and chronic inflammation: therapeutic implications of deucravacitinib.

Inflammation is increasingly recognized as a dynamic continuum rather than a dichotomous process, with acute cytokine storm and chronic inflammation representing interconnected immunopathological states. While acute hyperinflammation is driven by rapid cytokine amplification and innate immune activation, failure of resolution mechanisms facilitates transition toward persistent immune dysregulation. Central to this continuum is the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, with tyrosine kinase 2 (TYK2) functioning as a critical regulatory node integrating signals from type I interferons, interleukin-12, and interleukin-23. This review provides a mechanistic synthesis of the molecular events underlying cytokine storm, including immune cell activation, cytokine network architecture, and intracellular signaling cross-talk, and delineates how these processes evolve into chronic inflammation through immune cell reprogramming, epigenetic modifications, and loss of immune tolerance. Particular emphasis is placed on the role of TYK2 in bridging innate and adaptive immune responses, thereby sustaining inflammatory signaling across disease stages. The therapeutic implications of targeting TYK2 are highlighted through detailed evaluation of deucravacitinib, a selective allosteric inhibitor that modulates TYK2 signaling with high specificity. Clinical trial data demonstrate its efficacy and favorable safety profile in psoriasis and other immune-mediated disorders, positioning it as a promising strategy for precision immunomodulation. Overall, this review underscores TYK2 as a central mediator of inflammatory progression and a viable therapeutic target for interrupting the transition from acute hyperinflammation to chronic disease.