Characterization of psoriasiform dermatitis induced by systemic injection of interleukin‐23 minicircles in mice

Leys, Laura; Wang, Yibing; Paulsboe, Stephanie; Edelmayer, Rebecca M.; Salte, K.; Wetter, J.; Namovic, Marian T.; Phillips, Lucy; Dunstan, Robert W.; Gauvin, Donna M.; Donnelly‐Roberts, Diana L.; Su, Zhi; Honoré, Prisca; McGaraughty, Steve

doi:10.1111/1346-8138.14899

Cited by 12 publications

(19 citation statements)

References 44 publications

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“…Gene expression analysis by qPCR showed elevated expression of Tnf , Il1b , Il17a , and Il22 in the colon of IL-23 EEV injected mice ( Fig 2C ). Consistent with previous reports [ 17 – 20 ] we observed erythema and scaling of the skin of the ears and paws. H&E stained ear sections showed hyperplasia of the epithelial layer, thickening and inflammatory infiltration of the dermis ( Fig 2D ).…”

Section: Resultssupporting

confidence: 93%

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The impact of genetic background and sex on the phenotype of IL-23 induced murine spondyloarthritis

et al. 2021

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Background Overexpression of IL-23 in adult mice by means of hydrodynamic tail vein injection of IL-23 minicircles has been reported to result in spondyloarthritis-like disease. The impact of genetic background and sex on the disease phenotype in this model has not been investigated. Methods We compared male B10.RIII mice with male C57BL/6 mice, and male with female B10.RIII mice after hydrodynamic injection of IL-23 enhanced episomal vector (EEV) at 8–12 weeks of age. We monitored clinical arthritis scores, paw swelling, and body weight. Animals were euthanized after two weeks and tissues were harvested for histology, flow cytometry and gene expression analysis. Serum cytokine levels were determined by ELISA. Findings Male B10.RIII mice developed arthritis in the forepaws and feet within 6 days after IL-23 EEV injection; they also exhibited psoriasis-like skin disease, colitis, weight loss, and osteopenia. In contrast to previous reports, we did not observe spondylitis or uveitis. Male C57BL/6 mice injected with IL-23 EEV had serum IL-23 levels comparable with B10.RIII mice and developed skin inflammation, colitis, weight loss, and osteopenia but failed to develop arthritis. Female B10.RIII mice had more severe arthritis than male B10.RIII mice but did not lose weight. Conclusions The phenotype of IL-23 induced disease in mice is controlled by genetic background and sex of the animals. The development of extra-articular manifestations but absence of arthritis in C57BL/6 mice suggests that organ-specificity of IL-23 driven inflammation is genetically determined. The mechanisms behind the strain-specific differences and the sexual dimorphism observed in this study may be relevant for human spondyloarthritis and warrant further exploration.

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Section: Resultssupporting

confidence: 93%

“…Antibody-mediated depletion of γδ T cells ameliorated the arthritis phenotype [ 19 ]. The development of psoriasis-like skin disease after hydrodynamic injection of IL-23 minicircles has been reported by several groups [ 17 , 20 , 21 ]. Other extra-articular SpA phenotypes have been studied less thoroughly.…”

Section: Introductionmentioning

confidence: 99%

The impact of genetic background and sex on the phenotype of IL-23 induced murine spondyloarthritis

et al. 2021

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“…Gene expression analysis by qPCR showed elevated expression of Tnf, Il1b, Il17a , and Il22 in the colon of IL-23 EEV injected mice (Fig 2C). Consistent with previous reports [13–15, 22] we observed erythema and scaling of the skin of the ears and paws. H&E stained ear sections showed hyperplasia of the epithelial layer, thickening and inflammatory infiltration of the dermis (Fig 2D).…”

Section: Resultssupporting

confidence: 93%

The impact of genetic background and sex on the phenotype of IL-23 induced murine arthritis

Haley

Matmusaev

Hossain

et al. 2021

Preprint

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Background Overexpression of IL-23 in adult mice by means of hydrodynamic tail vein injection of IL-23 minicircles has been reported to result in spondyloarthritis-like disease. The impact of genetic background and sex on the disease phenotype in this model has not been investigated. Methods We compared male B10.RIII mice with male C57BL/6 mice, and male with female B10.RIII mice after hydrodynamic injection of IL-23 enhanced episomal vector (EEV) at 8-12 weeks of age. We monitored clinical arthritis scores, paw swelling, and body weight. Animals were euthanized after two weeks and tissues were harvested for histology, flow cytometry and gene expression analysis. Serum cytokine levels were determined by ELISA. Findings Male B10.RIII mice developed arthritis in the forepaws and feet within 6 days after IL-23 EEV injection; they also exhibited psoriasis-like skin disease, colitis, weight loss, and osteopenia. In contrast to previous reports, we did not observe spondylitis or uveitis. Male C57BL/6 mice injected with IL-23 EEV had serum IL-23 levels comparable with B10.RIII mice and developed skin inflammation, colitis, weight loss, and osteopenia but failed to develop arthritis. Female B10.RIII mice had more severe arthritis than male B10.RIII mice but did not lose weight. Conclusions Systemic IL-23 overexpression results in spondyloarthritis-like disease in B10.RIII mice. The development of extra-articular manifestations but absence of arthritis in C57BL/6 mice suggests organ-specific genetic control mechanisms of IL-23 driven inflammation. Discrepancies regarding the phenotype of IL-23 induced disease in different labs and the sexual dimorphism observed in this study warrant further exploration.

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“…Other experimental models function via induction of elevated levels of dermal IL-23, which in turn activates IL-23R-expressing dermal lymphocytes including γδ17 cells, αβ T cells, and ILCs. This may be achieved directly by intradermal injection of IL-23 (Gauld et al, 2018;Rizzo et al, 2011), or via increased systemic levels of IL-23 (Leys et al, 2019), although human psoriasis is not usually accompanied by increased serum levels of IL-23 (Bai et al, 2017). The most widely used experimental model is topical application of the TLR7/8 agonist imiquimod (Aldara; Gilliet et al, 2004;van der Fits et al, 2009), which induces the innate activation of dermal DCs (van der Fits et al, 2009).…”

Section: Dysregulation Of Il-17mentioning

confidence: 99%

Interleukin-17 cytokines: Effectors and targets in psoriasis—A breakthrough in understanding and treatment

Prinz

Sandrock

Mrowietz³

2019

Journal of Experimental Medicine

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The IL-17 cytokine family comprising IL-17A to IL-17F and receptor subunits IL-17RA to IL-17RE represents a genetically ancient intercellular network regulating local tissue homeostasis. Its pivotal role in antifungal defense and its central position in the pathogenesis of inflammatory diseases including psoriasis were discovered only relatively late in the early 2000s. Since the connection of dysregulated IL-17 and psoriasis pathogenesis turned out to be particularly evident, a number of monoclonal antibodies targeting IL-17 pathways have been approved and are used as first line treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis, and further agents are currently in clinical development.

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Characterization of psoriasiform dermatitis induced by systemic injection of interleukin‐23 minicircles in mice

Cited by 12 publications

References 44 publications

The impact of genetic background and sex on the phenotype of IL-23 induced murine spondyloarthritis

The impact of genetic background and sex on the phenotype of IL-23 induced murine spondyloarthritis

The impact of genetic background and sex on the phenotype of IL-23 induced murine arthritis

Interleukin-17 cytokines: Effectors and targets in psoriasis—A breakthrough in understanding and treatment

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