IL-31 targets the hair follicle bulge across species and restrains hair regeneration in mice

Here, reanalysis of public single-cell RNA-sequencing datasets and RNAscope identified Il31ra expression predominantly in the bulge and secondary hair germ (sHG) of mouse hair follicles and in the bulge compartment of human hair follicles. In isolated mouse keratinocytes, recombinant IL-31 (rIL-31) induced a bulge-enriched JAK-STAT–associated transcriptional response.

In vivo rIL-31 administration activated STAT3, STAT5, and ERK1/2 in mouse bulge/sHG cells, and these responses were lost in keratinocyte-specific Il31ra-deficient mice. In a hair plucking–induced anagen model, continuous rIL-31 administration delayed anagen progression in control mice but not in keratinocyte-specific Il31ra-deficient mice. Parallel analyses of human scalp skin demonstrated that IL31RA is similarly enriched in the bulge compartment.