A new study explains how UV exposure induces immunosuppression. Previous studies showed that UV-induced immunosuppression is caused by regulatory T cells (T reg cells). On page 173 , Schwarz et al. now show that the development of T reg cells requires DNA damage to DCs called Langerhans cells (LCs).
Mice exposed to UV light are rendered unresponsive to antigens applied to skin because of the induction of T reg cells, which interfere with activation of effector T cells in response to antigen. IL-12, a cytokine produced by LCs, can both prevent the establishment of the unresponsive state and can also reverse established tolerance when provided in combination with antigen stimulation. Schwarz et al. showed in a previous study that IL-12 also promotes DNA repair, but it was unclear how (or if) these functions of IL-12 related to one another.
The group now shows that the prevention of UV-induced immunosuppression relies on DNA repair. Mice that lacked the DNA repair machinery became immunocompromised after UV exposure even after they were given IL-12. In wild-type mice, IL-12 protected against immunosuppression.
Thus, IL-12 interference with immunosuppression appears to be dependent on its induction of DNA repair. The authors suggest that DNA damage may change the costimulatory molecules expressed on LCs, thus altering their stimulatory profile away from effector T cells and toward T reg cells.