Abstract
So far, thymus involution in adults is believed to be irreversible, and endogenous innovation for thymus-related immunodeficiency remains to be an intractable puzzle. With the expectation of addressing this dilemma, human ovarian surface epithelium (OSE) has been reengineered as epithelial-mesenchymal transition (EMT)-tridimensional-spheroid biologics (ETSB) using a dynamic EMT-3D-floating system along with 160 Gy X-ray-amelioration, which inoculates subcutaneously into aging rhesus and athymic Balb/c (nu/nu) mice. Herein, it is bioinformatically validated that ETSB can reset Clock/Arntl-Per3/Tim molecule rhythm dynamics to re-prime thymus residual (parathyroid or fatty-like invalid vesicles yet no thymic architecture) to evolutionary transcription with overall cortex-medulla endogenized by TECs undergoing MET/EMT reversion. Rhythm dynamics immediately resettles the bHLH-LTβR-NFκB-RelA/B loop as a cascade to provoke the core immune microenvironment for multifunctional innovation of dynamic TCR orchestration, with harmonious naïve T-subsets and TRECs renewals (P < 0.005). Subsequently, peripheral biological burden and tumor metastasis dynamics are addressed by innovative TCR-defense/attack dynamics quickly (P < 0.005 vs Control), yet without autoimmune indication to hosts. Moreover, a functional blockade of core-rhythm dynamics deeply impedes the endogenous innovation of invalid thymus residual. Thus this study may help pioneer a prospective strategy to innovate panoramic central-peripheral immune microenvironments and defense dynamics for immune-deficient/aging victims.