Regulation of IL-22BP in psoriasis

Voglis, Stefanos; Moos, Sonja; Kloos, Luise; Wanke, Florian; Zayoud, Morad; Pelczar, Penelope; Giannou, Anastasios D.; Pezer, Silvia; Albers, M.; Luessi, Felix; Huber, Samuel; Schäkel, Knut; Kurschus, Florian C.

doi:10.1038/s41598-018-23510-3

Cited by 21 publications

(24 citation statements)

References 35 publications

(57 reference statements)

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“…Acanthosis was shown to be dependent on IL-22, because it affects the differentiation of keratinocytes (Boniface et al, 2005;Ma et al, 2008;Wolk et al, 2006). In line with that, we recently showed that the IL-22 inhibitor IL-22BP is down-regulated in skin of psoriasis patients compared with skin from healthy patients, enabling IL-22's function in the disease (Voglis et al, 2018). Here, we found that the cytokine IL-22 was not up-regulated in mice lacking an IL-17 response in KCs after IMQ treatment.…”

Section: Discussionsupporting

confidence: 59%

Imiquimod-Induced Psoriasis in Mice Depends on the IL-17 Signaling of Keratinocytes

Moos

Mohebiany

Waisman

et al. 2019

Journal of Investigative Dermatology

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138

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The pathology of psoriasis strongly depends on IL-17A. Monoclonal antibodies blocking either the cytokine or its receptor are among the most efficient treatments for psoriatic patients. Keratinocytes can be activated upon exposure to IL-17A and tumor necrosis factor-a and secrete secondary cytokines and chemokines in the inflamed skin. In psoriasis and its imiquimod-induced mouse model, a strong skin infiltration of neutrophils and inflammatory monocytes can be observed. However, to date, it is not clear how exactly those cellular populations are attracted to the skin and how they contribute to the pathogenesis of the disease. To define the crucial cell type responding to IL-17 and initiating the downstream pathology in psoriasis-like dermatitis, we used mice specifically lacking the IL-17 receptor (IL-17RA) in different cell types. Deletion of IL-17RA in T cells or myeloid had no impact on disease development. Only deletion of this receptor in keratinocytes reflected the full-body deletion of IL-17RA, resulting in strongly reduced dermatitis development. Imiquimod treatment of those IL-17 signalingedeficient mice maintained high monocytic infiltration but failed to attract neutrophils into the skin. We conclude that keratinocytes are a critical cellular target for IL-17Aemediated neutrophil attraction and psoriasis development.

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Section: Discussionsupporting

confidence: 59%

Imiquimod-Induced Psoriasis in Mice Depends on the IL-17 Signaling of Keratinocytes

Moos

Mohebiany

Waisman

et al. 2019

Journal of Investigative Dermatology

Self Cite

138

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show abstract

“…They noted reduced expression of IL-22BP in mouse-model as well as in patients with psoriasis. They concluded that regulation of IL-22BP is a key step in the development of skin inflammation 47 . While the effect of IL-22BP is reversed in skin disease, its ability to regulate inflammation through action on IL-22 is consistent with our findings.…”

Section: Discussionmentioning

confidence: 99%

IL-22-binding protein exacerbates influenza, bacterial super-infection

et al. 2019

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Secondary bacterial pneumonia is a significant complication of severe influenza infection and Staphylococcus aureus and Streptococcus pneumoniae are the primary pathogens of interest. IL-22 promotes S. aureus and S. pneumoniae host defense in the lung through epithelial integrity and induction of antimicrobial peptides and is inhibited by the soluble decoy receptor IL-22 binding protein (IL-22BP). Little is known about the effect of the IL-22/IL-22BP regulatory pathway on lung infection, and it has not been studied in the setting of super-infection. We exposed wild-type and IL-22BP −/− mice to influenza A/PR/8/34 for six days prior to infection with S. aureus (USA300) S. pneumoniae . Super-infected IL-22BP −/− mice had decreased bacterial burden and improved survival compared to controls. IL-22BP −/− mice exhibited decreased inflammation, increased lipocalin 2 expression, and deletion of IL-22BP was associated with preserved epithelial barrier function with evidence of improved tight junction stability. Human bronchial epithelial cells treated with IL-22Fc showed evidence of improved tight junctions compared to untreated cells. This study revealed that IL-22BP −/− mice are protected during influenza, bacterial super-infection, suggesting that IL-22BP has a pro-inflammatory role and impairs epithelial barrier function likely through interaction with IL-22

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“…There it blocks IL-22 signaling through the follicle-associated epithelium (FAE), allowing for reduced expression of mucin and antimicrobial peptides at a key Ag sampling locale. In DCs, IL-22BP is upregulated by retinoic acid (65) and downregulated by IL-18, inflammasome activation, or PGE 2 (66,67). This makes IL-22BP a scientifically interesting protein, as the majority of proteins studied in DC biology are upregulated, not downregulated, upon inflammation.…”

Section: How Does Il-22 Binding Protein Regulate Il-22 Biology?mentioning

confidence: 99%

IL-22: There Is a Gap in Our Knowledge

Zenewicz

2018

ImmunoHorizons

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IL-22 is a critical cytokine in modulating tissue responses during inflammation. IL-22 is upregulated in many chronic inflammatory diseases, making IL-22 biology a potentially rewarding therapeutic target. However, this is complicated by the dual-natured role of IL-22 in inflammation, as the cytokine can be protective or inflammatory depending on the disease model. Although scientific interest in IL-22 has increased considerably in the past 10 y, there is still much we do not know about the environmental, cellular, and molecular factors that regulate the production and function of this cytokine. A better understanding of IL-22 biology will allow us to develop new or improved therapeutics for treating chronic inflammatory diseases. In this article, I will highlight some of the outstanding questions in IL-22 biology.

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Regulation of IL-22BP in psoriasis

Cited by 21 publications

References 35 publications

Imiquimod-Induced Psoriasis in Mice Depends on the IL-17 Signaling of Keratinocytes

Imiquimod-Induced Psoriasis in Mice Depends on the IL-17 Signaling of Keratinocytes

IL-22-binding protein exacerbates influenza, bacterial super-infection

IL-22: There Is a Gap in Our Knowledge

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