Evidence that AD is driven by multiple immune axes extending beyond the Th2 polarization has resulted in therapies targeting additional pathways, including the Th22, Th17/IL-23, and JAK-STAT pathways.
Ustekinumab, a human monoclonal IgG1 antibody targeting the p40-subunit shared by interleukin (IL)12 and IL-23, represents a potential treatment for atopic dermatitis (AD).
Although AD is predominantly associated with type 2 immune responses, activation of other cytokine pathways including T<sub>H</sub>1, T<sub>H</sub>22, and T<sub>H</sub>17/IL-23 has been reported, suggesting potential therapeutic targets and provide a rationale for treatment with novel biologics.
IL-23-injected, NC/Nga, and oxazolone-challenged mice show the largest homology with our human meta-analysis-derived AD transcriptome (37%, 18%, 17%, respectively).
AD-MSCs showed an upregulation of many Th1/Th17 cytokines [interleukin (IL)-6, IL-8, IL-12, IL-13, IL-17A, IL-17F, transforming growth factor-β, interferon-γ], while Th2 chemokines (IL-2, IL-4, IL-5, IL-23A) were downregulated in AD-MSCs.
As the IFN-gamma-inducing cytokines IL-12 and IL-23 utilize IL-12Rbeta1 as part of their receptors, it is possible that polymorphic variants of the IL-12Rbeta1 (IL12RB1) gene might determine an individual's susceptibility to AD.