Photoaging: UV radiation-induced inflammation and immunosuppression accelerate the aging process in the skin

Abstract

Background: Excessive exposure of the skin to UV radiation (UVR) triggers a remodeling of the immune system and leads to the photoaging state which is reminiscent of chronological aging. Over 30 years ago, it was observed that UVR induced an immunosuppressive state which inhibited skin contact hypersensitivity.

Methods: Original and review articles encompassing inflammation and immunosuppression in the photoaging and chronological aging processes were examined from major databases including PubMed, Scopus, and Google Scholar.

Results: Currently it is known that UVR treatment can trigger a cellular senescence and inflammatory state in the skin. Chronic low-grade inflammation stimulates a counteracting immunosuppression involving an expansion of immunosuppressive cells, e.g., regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC), and regulatory dendritic cells (DCreg). This increased immunosuppressive activity not only suppresses the function of effector immune cells, a state called immunosenescence, but it also induces bystander degeneration of neighboring cells. Interestingly, the chronological aging process also involves an accumulation of pro-inflammatory senescent cells and signs of chronic low-grade inflammation, called inflammaging. There is also clear evidence that inflammaging is associated with an increase in anti-inflammatory and immunosuppressive activities which promote immunosenescence.

Conclusion: It seems that photoaging and normal aging evoke similar processes driven by the remodeling of the immune system. However, it is likely that there are different molecular mechanisms inducing inflammation and immunosuppression in the accelerated photoaging and the chronological aging processes.

Keywords: Aging; Anti-inflammatory; Carcinogenesis; Lifespan; UVA; UVB.

Fig. 1

The pathogenesis of UVR-induced photoaging in the skin. UVR exposure induces damages in DNA and ECM of the skin. UVR also enhances the generation of ROS/RNS compounds and thus it promotes oxidative stress. UVR-induced alterations elicit inflammatory state in the skin. Subsequently, inflammation stimulates the expansion of immunosuppressive cells in the skin, thus counteracting the inflammatory state. The expansion of Tregs, MDSCs, Bregs, and DCregs enhances immunosuppressive activity in the skin. There are several mechanisms which can evoke the immunosuppressive state in the skin: (i) UVR stimulates the generation of FICZ and cis-UCA compounds, (ii) inflammation stimulates the synthesis of KYN and KYNA, (iii) inflammation activates COX-2 and increases the generation of PGE2, (iv) immunosuppressive cells secrete anti-inflammatory cytokines, such as IL-10 and TGF-β, and (v) immune cells secrete amphiregulin which exerts a suppressive activity on Tregs. The activation of UVR-inflammation-immunosuppression pathway promotes the senescence of immune and non-immune cells in the skin. Senescent cells express a pro-inflammatory secretory phenotype (SASP) which is driving the pathological alterations evident in the skin. Chronic inflammation and the counteracting immunosuppression cause degenerative alterations in the skin inducing the photoaging state. Breg regulatory B cell, COX-2 cyclo-oxygenase-2, DCreg regulatory dendritic cell, ECM extracellular matrix, FICZ 6-formylindolo[3,2-b]carbazole, IL-10 interleukin-10, KYN kynurenine, KYNA kynurenic acid, MDSC myeloid-derived suppressor cell, PGE2 prostaglandin E2, SASP senescence-associated secretory phenotype, TGF-β transforming growth factor-β, Treg, regulatory T cell, UCA urocanic acid, UVR ultraviolet radiation