title: The DNA damage response induces antigen presenting cell-like functions in fibroblasts.
abstract: The DNA damage response (DDR) alerts the immune system to the danger posed by DNA damage through the induction of damage-associated molecular pattern molecules, chemokines, and ligands for activating immune receptors such as lymphocyte function-associated antigen 1 (LFA-1), NKG2D, and DNAX accessory molecule 1 (DNAM-1). Here we provide evidence that OVA(257-264) -pulsed fibroblasts gain the ability to activate naïve OT-I CD8(+) T cells in response to DNA damage. The ability of fibroblasts to activate OT-I CD8(+) T cells depended on the upregulation of ICAM-1 on fibroblasts and DNAM-1 expression of CD8(+) T cells. OVA(257-264) -pulsed fibroblasts were able to induce a protective T-cell response against B16-OVA cells in a DDR-dependent manner. Hence, the DDR may alert the immune system to the presence of potentially dangerous cells by upregulating the expression of ligands that can induce the activation of innate and adaptive immune cells.
authors.affiliation: Immunology Programme, Department of Microbiology, National University of Singapore, Singapore.
authors.forename: Melissa Li Fang
authors.initials: ML
authors.lastname: Tang
authors.forename: Muznah Khatoo Nazar
authors.initials: MK
authors.lastname: Khan
authors.forename: John Ludovic
authors.initials: JL
authors.lastname: Croxford
authors.forename: Kar Wai
authors.initials: KW
authors.lastname: Tan
authors.forename: Veronique
authors.initials: V
authors.lastname: Angeli
authors.forename: Stephan
authors.initials: S
authors.lastname: Gasser
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D064007:Ataxia Telangiectasia Mutated Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D044482:Benzeneacetamides / Q000276:immunology / Q000494:pharmacology; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D003561:Cytarabine / Q000276:immunology / Q000494:pharmacology; D004249:DNA Damage / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D044482:Benzeneacetamides; D000098862:T Lineage-Specific Activation Antigen 1; C512273:CGK 733; D003561:Cytarabine; D018799:Intercellular Adhesion Molecule-1; D010047:Ovalbumin; C576897:Atr protein, mouse; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D013890:Thiourea
keywords: Adaptive immunity; Antigen-presenting cell; Chemotherapy; DNA damage; Fibroblasts