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- Title
IL-1 signalling determines the fate of skin grafts expressing non-self protein in keratinocytes.
- Authors
Hadis, Usriansyah; Leggatt, Graham R.; Thomas, Ranjeny; Frazer, Ian H.; Kovacs, Eva M.
- Abstract
Please cite this paper as: IL-1 signalling determines the fate of skin grafts expressing non-self protein in keratinocytes. Experimental Dermatology 2010; 19: 723-729. Abstract: Although IL-1 is a known inflammatory cytokine during pathogen infection, the role of IL-1 in skin graft rejection, particularly where foreign antigen is expressed exclusively in keratinocytes, is less understood. Here, we use a syngeneic skin graft system, where antigens are expressed in epithelial cells via either a keratin 14 or keratin 5 promoter, to explore the role of IL-1 in graft rejection and induction of epithelial antigen-specific effector CD8+ T-cell function. Keratin 5 ovalbumin (K5mOVA) transgenic skin grafts destined for rejection demonstrated increased expression of IL-1β and its receptors compared to K14 HPV16 E7 transgenic grafts that do not reject spontaneously. Rejection of OVA grafts lacking the IL-1 receptor (IL-1R1) was delayed and associated with decreased numbers of antigen-specific CD8 T cells. In contrast, K14E7 grafts survived on immunocompetent, syngeneic recipients with decreased graft levels of IL-1β and IL-1R1 and 2. However, in the absence of the IL-1 receptor antagonist, IL-1Ra, skin grafts were spontaneously rejected and an E7-specific CD8 T-cell response was primed. Thus, expression of the HPV16E7 oncoprotein in epithelial cells prevents IL-1β-associated skin graft rejection and induction of antigen-specific CD8 T-cell responses. Enhancing IL-1β signalling, via blocking of the IL-1 receptor antagonist, may represent an alternative strategy for treatment of HPV16E7-associated cancers.
- Subjects
KERATINOCYTES; SKIN grafting; GRAFT rejection; ANTIGENS; SKIN inflammation
- Publication
Experimental Dermatology, 2010, Vol 19, Issue 8, p723
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/j.1600-0625.2010.01092.x