IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation.
Psoriasis is a chronic skin disease resulting from the dysregulated interplay between keratinocytes and infiltrating immune cells. We report on a psoriasis-like disease model, which is induced by the transfer of CD4(+)CD45RB(hi)CD25(-) cells to pathogen-free scid/scid mice. Psoriasis-like lesions had elevated levels of antimicrobial peptide and proinflammatory cytokine mRNA. Also, similar to psoriasis, disease progression in this model was dependent on the p40 common to IL-12 and IL-23. To investigate the role of IL-22, a Th17 cytokine, in disease progression, mice were treated with IL-22-neutralizing antibodies. Neutralization of IL-22 prevented the development of disease, reducing acanthosis (thickening of the skin), inflammatory infiltrates, and expression of Th17 cytokines. Direct administration of IL-22 into the skin of normal mice induced both antimicrobial peptide and proinflammatory cytokine gene expression. Our data suggest that IL-22, which acts on keratinocytes and other nonhematopoietic cells, is required for development of the autoreactive Th17 cell-dependent disease in this model of skin inflammation. We propose that IL-22 antagonism might be a promising therapy for the treatment of human psoriasis.
Ma
Hak-Ling
HL
Inflammation and Biological Technologies, Wyeth Research, Cambridge, Massachusetts 02140, USA.
Liang
Spencer
S
Li
Jing
J
Napierata
Lee
L
Brown
Tom
T
Benoit
Stephen
S
Senices
Mayra
M
Gill
Davinder
D
Dunussi-Joannopoulos
Kyriaki
K
Collins
Mary
M
Nickerson-Nutter
Cheryl
C
Fouser
Lynette A
LA
Young
Deborah A
DA
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D003872:Dermatitis / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018664:Interleukin-12 / Q000494:pharmacology; D053762:Interleukin-12 Subunit p40 / Q000037:antagonists & inhibitors; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D011565:Psoriasis / Q000276:immunology*; D012867:Skin / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D000097043:Interleukin-22
D019138:Antibodies, Blocking; D016207:Cytokines; D018664:Interleukin-12; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D007378:Interleukins; D008070:Lipopolysaccharides; D000097043:Interleukin-22