Human Susceptibility to UVB-Induced Immunosuppression Is Associated with UVB-Induced Activation of the DAMP Pathway in the Skin.

BACKGROUND

Although ultraviolet B (UVB) radiation-induced immunosuppression is considered a key risk factor for skin cancer, individual susceptibility varies, and its mechanisms remain not fully understood.

OBJECTIVE

The current study collected skin biopsies from healthy volunteers before and after UVB radiation and linked UVB-induced effects in the skin to immunosuppression in the same individuals.

METHODS

A total of 62 healthy volunteers were recruited and randomly assigned to three groups: negative, positive, and UVB-exposed. Diphenylcyclopropenone was applied topically to induce contact hypersensitivity (CHS) responses. Skin punch biopsies were collected before and after UVB for analysis.

RESULTS

UVB exposure significantly suppressed CHS compared to the positive control. However, among 26 individuals, 7 (27%) were resistant (UVB-R), while the rest were susceptible (UVB-S) to UVB-induced immunosuppression. RNA-seq analysis of skin biopsies showed that UVB induced a higher level of immunosuppressive inflammation in UVB-S than in UVB-R individuals. Further analysis showed that UVB significantly activated the damage-associated molecular patterns only in UVB-S, but not in UVB-R individuals.

CONCLUSION

Given the role of DAMP pathways in the development of inflammation, the results reveal a previously unrecognized mechanism: UVB-induced activation of DAMP pathways is linked to UVB-induced immunosuppressive inflammation in skin and susceptibility to immunosuppression in humans.