IL-1RL2 and its ligands contribute to the cytokine network in psoriasis.
Psoriasis is a common immune-mediated disease in European populations; it is characterized by inflammation and altered epidermal differentiation leading to redness and scaling. T cells are thought to be the main driver, but there is also evidence for an epidermal contribution. In this article, we show that treatment of mouse skin overexpressing the IL-1 family member, IL-1F6, with phorbol ester leads to an inflammatory condition with macroscopic and histological similarities to human psoriasis. Inflammatory cytokines thought to be important in psoriasis, such as TNF-α, IL-17A, and IL-23, are upregulated in the mouse skin. These cytokines are induced by and can induce IL-1F6 and related IL-1 family cytokines. Inhibition of TNF or IL-23 inhibits the increased epidermal thickness, inflammation, and cytokine production. Blockade of IL-1F6 receptor also resolves the inflammatory changes in human psoriatic lesional skin transplanted onto immunodeficient mice. These data suggest a role for IL-1F family members in psoriasis.
Blumberg
Hal
H
Amgen, Seattle, WA 98119, USA. halb@novonordisk.com
Dinh
Huyen
H
Dean
Charles
C
Trueblood
Esther S
ES
Bailey
Keith
K
Shows
Donna
D
Bhagavathula
Narasimharao
N
Aslam
Muhammad Nadeem
MN
Varani
James
J
Towne
Jennifer E
JE
Sims
John E
JE
D000818:Animals; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D053727:Interleukin-18 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017472:Receptors, Interleukin-1 / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; C508573:Il18r1 protein, mouse; D007375:Interleukin-1; D053727:Interleukin-18 Receptor alpha Subunit; D008024:Ligands; D017472:Receptors, Interleukin-1