Transcriptional choreography of skin cells by liganded immodulin peptides

Abstract

SCDIs mediate transcriptional effects through RXR transcriptional complexes. Biodistribution studies show that, when applied transdermally to rats using a nanoemulsion, SCDIs rapidly partition to skin tissue resulting in a 3-10× enrichment relative to plasma even at skin locations distant from the site of application. Transcriptional governance of circuits relevant to tissue repair, such as CD169+ macrophage differentiation, previously shown to drive differentiation of CD4+ Tcells into iTregs, can be increased by SCDIs with an RARα/β ligand; IL-19, IL-22 and IL-24 production by HaCaT keratinocytes with an RARγ agonist; and FGF7/KGF-1, TGFβ and COL1A1 by a partial PPARγ ligand in dermal fibroblasts. Myoblast or myofibroblast differentiation can be stimulated by a PPARα ligand. Sequential controlled-release of the appropriate SCDIs applied as a single dose, especially with transferrin as carrier, can drive transcriptional choreography in the context of a multi-stage biological process in tissue.

Dependencies are inferred from the claim text.