Tetrahydroxy stilbene glucoside promotes hair regeneration by inducing Th22 cell differentiation

Hair plays an important roles in both local protection and information transmission. But as a widespread problem, the existing therapies of hair loss are limited. 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-Glucoside (Tetrahydroxy stilbene glucoside, TSG) is the main active compound of a hair promoting herb, Polygonum multiflorum Thunb., that has been used in China for over 1000 years. However, its role and mechanism of action remain unclear.

To investigate the promoting effect of TSG on hair growth and elucidate the mechanism by which TSG affects hair regeneration via Th22.

Mouse skin explants and 3D ex vivo culture systems were employed to screen substances of P. multiflorum for promoting hair growth. The hair regeneration effect of TSG was explored via mice model by subcutaneous injection. The changes of biological dynamics, hair regeneration, histomorphology of skin, and morphology of hair follicle were observed. T cell subsets in peripheral blood was analyzed by Flow cytometry. Network pharmacology was used to predict the mechanism of TSG, immunohistochemistry and immunofluorescence staining were used to analyzed the distribution of T cell subsets around hair follicles. IL-22BP was used to verify the role of Th22 cells in TSG regulating hair regeneration in mice.

Ex vivo organ experiments showed that compared with emodin and catechol, TSG could effectively promote the process of hair follicle transition from telogen to anagen, and make them rapidly proliferate and differentiate into hair matrix. TSG accelerated the hair growth in mice, increased the number of hair follicles and the proportion of CD4⁺ T cells in peripheral blood, unregulated the expression of CCR10 (Th22 marker) in the hair root sheath of hair follicle. Network pharmacology suggested TSG treatment was associated with T cell differentiation related signaling pathways, it could facilitated the differentiation and development of T cells around hair follicles, driving their transition to the Th22 subtype. IL-22BP confirmed that IL-22 secreted by activated Th22 cells is the key factor mediating hair regeneration promoted by TSG, which indirectly verifies that Th22 cells are the effector cells responsible for TSG-induced hair regeneration.

TSG accelerates the growth of mice hair follicles and promoting the regeneration of hair follicles by regulating the distribution and immune homeostasis of T cell subsets around hair follicles and promoting the differentiation and development of Th22 cells.