Redox, immune and genetic biomarker system for personalized treatments in colorectal cancer

Figure 1 Trx1/CD30 redox immune regulation. A: Trx1 oxidized form (-S-S-); Trx1 reduced form (-SH); RTrx1; NADPH. CD30 oxidized form (-S-S); CD30 reduced form (-SH); CD30L; NK, DC, monocytes, T cells, neutrophils, eosinophils and B cells. Trx1/CD30 preserves the healthy state during aging by inducing the integrate expression of IFNγ IL4, TGFβ, IL6, IL10 and IL2 cell pathways to direct Th differentiation to the respective subtypes (Th1, Th2, Treg, Th9, Th17). The cytokines in the cell environment activate specific transcription factors for the differentiation of the specific Th subsets. Th1 requires the T bet (Tbet); Th2 the GATA; Treg cells the Foxp3; Th17 the RORgt; Th9 the PU.1 bet. TGFβ activates the expression of Foxp3, which generates (↑) Treg cells. IL6 inhibits the TGFβ driven expression of Foxp3, and TGFβ together with IL6 activate the ROR-gt transcription factor, which triggers (↑) Th17 cells. Nevertheless IL2 inhibits (⊥) this induction. IL4 also inhibits TGFβ induction of the Foxp3 expression, but TGFβ together with IL4 activate the expression of the PU.1 transcription factor, which generates (↑) Th9 cells. IFNγ and IL2 inhibit (⊥) this generation; B: Deregulation (↓↑) between Trx1/RTrx1 levels and increase (↑) of the sCD30 level cause non-homeostasis of the redox-immune response and non-CD30 activation, which cause aging gender-specific disease generation. RTrx1: Thioredoxin1 reductase flavoprotein; NADPH: Nicotinamide adenine dinucleotide phosphate; CD30L: CD30 ligand; NK: Natural killer cells; DC: Dendritic cells; IFNγ: Interferon gamma; IL: Interleukin; TGFβ: Transforming growth factor beta; Foxp3: Forkhead box P3; RORgt: Retinoic acid-related orphan receptor gt.