IL-22 is required for Th17 cell–mediated pathology in a mouse model of psoriasis-like skin inflammation
Hak-Ling Ma, … , Lynette A. Fouser, Deborah A. Young
Hak-Ling Ma, … , Lynette A. Fouser, Deborah A. Young
Published January 17, 2008
Citation Information: J Clin Invest. 2008;118(2):597-607. https://doi.org/10.1172/JCI33263.
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Research Article Dermatology

IL-22 is required for Th17 cell–mediated pathology in a mouse model of psoriasis-like skin inflammation

Abstract

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+CD45RBhiCD25– 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.

Authors

Hak-Ling Ma, Spencer Liang, Jing Li, Lee Napierata, Tom Brown, Stephen Benoit, Mayra Senices, Davinder Gill, Kyriaki Dunussi-Joannopoulos, Mary Collins, Cheryl Nickerson-Nutter, Lynette A. Fouser, Deborah A. Young

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Figure 4

IL-22 neutralization prevents the development of skin lesions.

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IL-22 neutralization prevents the development of skin lesions. (A) Left ...
(A) Left panel shows the mean disease severity (±SEM) in recipient mice that were given 16 mg/kg of IL-22 (IL22-104) or isotype control antibody, i.p. once per week for 11 weeks. *P < 0.05 starting on day 26, comparing the 2 groups, with n = 10 mice. Right panel shows the disease severity scores at the end of the study. Data are representative of at least 2 independent experiments. (B and C) H&E-stained sections of ear tissue from recipients given an isotype control (left) or IL-22 antibody (right). Original magnification, ×200 (B) and ×400 (C). (D) Epidermal thickness and semiquantitative scoring of basilar papillae and inflammatory infiltrates in the indicated skin layers. A section from each mouse ear was scored as follows: 0, within normal limits; 1, minimal; 2, mild; 3, moderate; 4, marked; and 5, severe. Means ± SEM are shown, with n = 10 mice. (E and F) Representative immunohistochemical staining for CD11b+ (E) and CD4+ (F) in ear sections from recipients given isotype control antibody (left) or IL-22 antibody (right). Original magnification, ×400. (G) Mean disease severity in recipient mice after cell transfer and subsequent weekly treatment starting on day 14 with 16 mg/kg of IL-22 (IL22-103) or isotype control antibody (as indicated by arrow). *P < 0.05 on day 46 comparing the 2 groups (n = 10 mice). Right panel shows individual disease severity scores at the end of the study.