title: DNA damage, apoptosis and langerhans cells--Activators of UV-induced immune tolerance.
abstract: Solar UVR is highly mutagenic but is only partially absorbed by the outer stratum corneum of the epidermis. UVR can penetrate into the deeper layers of the epidermis, depending on melanin content, where it induces DNA damage and apoptosis in epidermal cells, including those in the germinative basal layer. The cellular decision to initiate either cellular repair or undergo apoptosis has evolved to balance the acute need to maintain skin barrier function with the long-term risk of retaining precancerous cells. Langerhans cells (LCs) are positioned suprabasally, where they may sense UV damage directly, or indirectly through recognition of apoptotic vesicles and soluble mediators derived from surrounding keratinocytes. Apoptotic vesicles will contain UV-induced altered proteins that may be presented to the immune system as foreign. The observation that UVR induces immune tolerance to skin-associated antigens suggests that this photodamage response has evolved to preserve the skin barrier by protecting it from autoimmune attack. LC involvement in this process is not clear and controversial. We will highlight some basic concepts of photobiology and review recent advances pertaining to UV-induced DNA damage, apoptosis regulation, novel immunomodulatory mechanisms and the role of LCs in generating antigen-specific regulatory T cells.
authors.affiliation: Department of Dermatology, The UAB Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL, USA. timares@uab.edu
authors.forename: Laura
authors.initials: L
authors.lastname: Timares
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Katiyar
authors.forename: Craig A
authors.initials: CA
authors.lastname: Elmets
mesh_terms: D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D006801:Humans; D007108:Immune Tolerance / Q000528:radiation effects*; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D014466:Ultraviolet Rays