IL-1 signalling determines the fate of skin grafts expressing non-self protein in keratinocytes

Hadis, Usriansyah, Leggatt, Graham R., Thomas, Ranjeny, Frazer, Ian H. and Kovacs, Eva M. (2010) IL-1 signalling determines the fate of skin grafts expressing non-self protein in keratinocytes. Experimental Dermatology, 19 8: 723-729. doi:10.1111/j.1600-0625.2010.01092.x

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Author Hadis, Usriansyah
Leggatt, Graham R.
Thomas, Ranjeny
Frazer, Ian H.
Kovacs, Eva M.
Title IL-1 signalling determines the fate of skin grafts expressing non-self protein in keratinocytes
Journal name Experimental Dermatology   Check publisher's open access policy
ISSN 0906-6705
1600-0625
1479-1250
Publication date 2010-08-01
Sub-type Article (original research)
DOI 10.1111/j.1600-0625.2010.01092.x
Volume 19
Issue 8
Start page 723
End page 729
Total pages 7
Editor Thomas A. Luger
Ralf Paus
Place of publication Copenhagen, Denmark
Publisher Munksgaard International Publishers
Language eng
Formatted 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.
© 2010 John Wiley & Sons A/S.
Keyword IL-1
IL-1Ra
Skin
Skin grafts
T cells
Interleukin-1 receptor antagonist
Dependent antibody-production
Adhesion molecule expression
T-cell-activation
Cutaneous inflammation
Cervical-cancer
Deficient mice
1 receptor
Antigen
IL-1-beta
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
UQ Diamantina Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 3 times in Scopus Article | Citations
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Created: Sun, 08 Aug 2010, 10:06:04 EST