Transcription‐Related Dynamics from Immune Disability into Endogenous Innovation

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/cnu/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.