O7 Skin microbiota promotes keratinocyte apoptosis and suppresses proliferation following ultraviolet radiation exposure in human skin in vivo
Wen Duan, Mark Farrar, Anne Chandidzura, Michael Peake, Bezaleel Mambwe, Abigail Langton, Andrew McBain, Lesley Rhodes, Catherine O’NeillAbstract
Introduction and aims
The skin and its resident microbiota are routinely exposed to ultraviolet radiation (UVR) from sunlight. Although UVR effects on skin are well described, it is not fully understood how the skin microbiota, an important modulator of skin immunity and barrier integrity, regulates the human cutaneous response to UVR exposure. We aimed to determine whether the human skin microbiota alters keratinocyte apoptosis and proliferation in vivo after UVR exposure.
Methods
Healthy volunteers [n = 10; Fitzpatrick skin types I–III; mean age 31.6 years (SD 2.47)] participated in a controlled clinical study. The right upper back was disinfected with 70% ethanol (we previously showed this to reduce skin microbiota for up to 6 h), then exposed to 80 mJ cm−2 erythemally weighted solar-simulated UVR. The contralateral nondisinfected sites were similarly exposed. Skin biopsies were collected from irradiated and matched unirradiated sites at 0.5 h and 24 h post-UVR exposure. Gene expression and pathway enrichment at 24 h postexposure was assessed by spatial transcriptomics (Xenium, n = 3). Keratinocyte apoptosis (TUNEL) and proliferation (Ki67) were quantified by immunostaining (n = 10) at 0.5 h and 24 h postexposure.
Results
At 24 h post-UVR exposure, keratinocytes from UVR-irradiated, disinfected skin showed relatively higher expression of cell-cycle/proliferation-associated genes, whereas keratinocytes from UVR-irradiated, nondisinfected skin showed relatively higher expression of apoptosis effector genes. Compared with nonirradiated skin, ingenuity pathway analysis predicted upregulation of cell-cycle/proliferation signalling in disinfected skin and TP53-related cell-death transcriptional signalling in nondisinfected skin. Consistent with this, UVR-irradiated, disinfected skin had significantly fewer TUNEL+ keratinocytes (P = 0.046) and significantly more Ki67+ keratinocytes (P = 0.042) than UVR-irradiated, nondisinfected skin.
Conclusions
Reduction of the skin microbiota alters human cutaneous response to UVR exposure at both transcriptomic and protein levels, indicating that the skin microbiota may promote keratinocyte apoptosis and suppress keratinocyte proliferation after UVR exposure. This broadens understanding of microbiota–host interactions in UVR-induced skin responses.