Innate immune sensors stimulate inflammatory and immunosuppressive responses to UVB radiation

Abstract

Almost 40 years from when it was first reported that UVB radiation exposure would modulate immune signaling, the photoimmunology field is still trying to understand the mechanisms by which UVB initiates inflammatory responses and modulates immune recognition. This commentary focuses on the ability of Toll-like receptors (TLRs), specifically TLR4 (Ahmad et al., 2014) and ligands such as damage-associated molecular patterns (DAMPs) released from injured cells to stimulate innate immune signaling and inflammatory cytokine production following UVB irradiation.

Figure 1. Innate immune signaling through damage-associated molecular patterns (DAMPs) in UVB-exposed skin

UVB-modified nucleic acids, as well as lipids and proteins, may act as DAMPs to stimulate innate immune signaling in responding cells. DAMPs are released from necrotic cells and taken up by adjacent cells to activate membrane and cytosolic innate immune sensors such as TLRs and cGAS. This initiates downstream signaling cascades that lead to the upregulation of cytokines involved in the inflammatory and immune responses of UVB exposure. cGAS, cGMP-AMP-synthase; TGF, transforming growth factor; TLR, Toll-like receptor; TNF, tumor necrosis factor.