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 1

Coadministration of IL-12 and LPS enhances the development of skin lesions in a CD4+CD45RBhi adoptive transfer model.

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Coadministration of IL-12 and LPS enhances the development of skin lesio...
(A) Disease progression in CB17 scid/scid recipient mice with or without (naive) adoptive transfer of 4 × 105 CD4+CD45RBhi sorted cells. The recipient mice with cell transfer were treated with saline or IL-12 (10 ng) plus LPS (20 μg) (i.p.) on day 1 and saline or IL-12 (10 ng) on day 3 (i.p.). *P < 0.05 starting from day 37 between the saline-treated group and the IL-12/LPS–treated group, both with cell transfer. (B) RNA was purified from an ear biopsy of each mouse within a group at the end of the study and evaluated by quantitative RT-PCR for the indicated cytokines. Results are reported as group means ± SEM, with n = 10 for each group. Data are representative of at least 2 independent experiments. *P < 0.05 between no-treatment group (naive) and saline-treated group with cell transfer; **P < 0.05 between no-treatment group (naive) and LPS plus IL-12–treated group with cell transfer; ***P value between saline and LPS plus IL-12 treated group is indicated.