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 2

Adoptive transfer of CD4+CD45RBhi T cells depleted of CD25+ Tregs enhances the development of skin lesions in scid/scid mice.

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Adoptive transfer of CD4+CD45RBhi T cells depleted of CD25+ Tregs enhanc...
(A) Representative images of psoriaform lesions in scid/scid mice induced by transfer of CD4+CD45RBhiCD25– T cells. The numbers correspond to the given disease severity scores. (B) Mean disease severity in mice after transfer of indicated cells or saline. Left: *P < 0.05 starting on day 21 between CD4+CD45RBhiCD25– and saline groups; #P < 0.05 starting on day 35 between CD4+CD45RBhi and saline; **P < 0.05 starting on day 49 between CD4+CD45RBhiCD25– and CD4+CD45RBhi (n = 10). Middle: Average Foxp3 gene expression in ear mRNA from indicated groups (n = 10). Right: Mean disease severity in scid/scid mice after transfer of T cells with or without indicated Treg numbers. *P < 0.05 between mice receiving 2 × 105 and no Tregs; **P < 0.05 between 0.4 × 105 and no Tregs. (C) H&E-stained ear (top panels) and back skin (bottom panels) sections from a mouse transferred with saline or CD4+CD45RBhiCD25– cells with parakeratosis (p), acanthosis (a), dermal inflammatory infiltrates (di), basilar papilla (bp), and epidermal microabscess (em) as indicated. Original magnification, ×400. (D) Intracellular cytokine staining was performed on pooled cervical lymph node cells collected from mice that received CD4+CD45RBhiCD25– T cells. Results shown are gated on CD4+ population. (E) Quantitative RT-PCR for the cytokines was performed on ear mRNA, with results reported as group means ± SEM (n = 10). Data are representative of at least 2 independent experiments.