IL-12

Interleukin-12 (IL-12) is a heterodimeric cytokine essential for cell-mediated immunity, promoting Th1 differentiation and interferon-γ production^[1][2][3]. Mechanistically, IL-12 signals through the IL-12 receptor complex composed of IL-12Rβ1 and IL-12Rβ2 subunits, activating the JAK-STAT pathway to drive T-cell and natural killer cell responses^[4][5]. In disease models, IL-12 contributes to the pathogenesis of autoimmune conditions such as Crohn’s disease, psoriasis, and experimental autoimmune encephalomyelitis, where its modulation alters inflammatory outcomes^[1][6][7]. Compared with related isoforms IL-23 and IL-27, IL-12 uniquely favors Th1 polarization while sharing the p40 subunit with IL-23, highlighting the importance of selective targeting in experimental and therapeutic settings^[8][4]. Pharmacological inhibition of IL-12 can occur via NF-κB blockade, modulation of Smad2/3 or JNK signaling, or through receptor antagonists, and these strategies have shown efficacy in reducing disease activity in both in vitro and in vivo models^{[9][5][10][11]}. IL-12-targeted therapies, including monoclonal antibodies like ustekinumab, provide research applications for dissecting immune pathways, assessing cytokine-mediated inflammation, and testing combinatory treatments with IL-23 or IL-17 inhibitors^[1][12][14]. Agonist forms of IL-12, such as homodimeric β2, reveal potential to enhance inflammatory responses in controlled experimental studies, offering insight into isoform-specific effects and pathway modulation^[9][8].