Skin Inflammation Induced by the Synergistic Action of IL-17A, IL-22, Oncostatin M, IL-1α, and TNF-α Recapitulates Some Features of Psoriasis

Guilloteau, Karline; Pâris, Isabelle; Pedretti, Nathalie; Boniface, Katia; Juchaux, Franck; Huguier, V.; Guillet, G.; Bernard, François‐Xavier; Lecron, Jean‐Claude; Morel, Franck

doi:10.4049/jimmunol.0902464

Cited by 290 publications

(275 citation statements)

References 49 publications

(63 reference statements)

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“…To study the possible immunomodulatory role of IL-37 in psoriasis in vitro, the keratinocyte cell line HaCaT was stimulated with proinflammatory cytokines (M5) to mimic the Th1/Th17/ Th22 inflammatory response between keratinocytes and immune cells in the pathogenesis of psoriasis (19). M5 activated the STAT3-, MAPK-, and NF-kB-signaling pathways (reinforced by C/EBP transcription factor activation induced by IL-17A), resulting in a synergistic effect on CXCL8, IL-6, and S100A7 production by human keratinocytes, which is effectively inhibited by IL-37, suggesting the harnessing effect of IL-37 in the autoimmune response.…”

Section: Discussionmentioning

confidence: 99%

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IL-37 Ameliorates the Inflammatory Process in Psoriasis by Suppressing Proinflammatory Cytokine Production

Teng

Wei

et al. 2014

The Journal of Immunology

154

132

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IL-37 is a potent inhibitor of innate immunity by shifting the cytokine equilibrium away from excessive inflammation. Psoriasis is thought to be initiated by abnormal interactions between the cutaneous keratinocytes and systemic immune cells, triggering keratinocyte hyperproliferation. In the current study, we assessed IL-37 in two well-known psoriasis models: a human keratinocyte cell line (HaCaT) and the keratin 14 VEGF-A–transgenic mouse model. First, we used the HaCaT cell line, which was transiently transfected with an overexpressing IL-37 vector, and tested the effect of IL-37 on these cells using a mixture of five proinflammatory cytokines. IL-37 was effective in suppressing the production of CXCL8, IL-6, and S100A7, which were highly upregulated by the mixture of five proinflammatory cytokines. Keratin 14 VEGF-A–transgenic mice were treated with plasmid coding human IL-37 sequence–formulated cationic liposomes, and we observed potent immunosuppressive effects over the 18-d period. In this model, we observed reduced systemic IL-10 levels, local IFN-γ gene transcripts, as well as mild mast cell infiltration into the psoriatic lesions of the mice. Immunohistochemical analysis indicated that IL-37 was expressed by effector memory T cells, as well as macrophages, in human psoriatic plaques. In conclusion, our studies strongly indicate that IL-37 plays a potent immunosuppressive role in the pathogenesis of both experimental psoriasis models in vitro and in vivo by downregulating proinflammatory cytokines. Importantly, our findings highlight new therapeutic strategies that can be designed to use this immunosuppressive anti-inflammatory cytokine in psoriasis and other inflammatory cutaneous diseases.

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Section: Discussionmentioning

confidence: 99%

“…Keratinocytes were stimulated with M5 to induce inflammation that recapitulates numerous features of psoriasis (19). Total RNA was isolated from keratinocytes at 0, 6, 12, and 24 h poststimulation with M5.…”

Section: Induction Of Psoriatic Model In Vitromentioning

confidence: 99%

IL-37 Ameliorates the Inflammatory Process in Psoriasis by Suppressing Proinflammatory Cytokine Production

Teng

Wei

et al. 2014

The Journal of Immunology

154

132

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“…S100A7 production is triggered by some bacterial components through PRRs and by proinflammatory cytokines (2,22,56). It is constitutively expressed in ocular surface epithelium and increases in corneal epithelial cell culture upon stimulation with bacterial antigens and proinflammatory cytokines (IL-1␤, tumor necrosis factor alpha [TNF-␣]) (18).…”

Section: Discussionmentioning

confidence: 99%

Active Trachoma Is Associated with Increased Conjunctival Expression ofIL17Aand Profibrotic Cytokines

et al. 2011

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The immunological basis of scarring trachoma is not well understood. It is unclear whether it is driven primarily through cell-mediated adaptive or epithelial-cell-derived innate responses. The purpose of this study was to investigate the expression of the inflammatory and fibrogenic mediators which may be involved. We conducted a cross-sectional survey of children living in an untreated trachoma-endemic community in Tanzania. The children were examined for signs of trachoma, and swabs were collected for bacteriological culture and RNA and DNA isolation. Chlamydia trachomatis was detected by the Amplicor PCR test. The expression of the following genes was measured by quantitative reverse transcription-PCR (RT-PCR): S100A7, IL1B, IL17A, IL23A, CXCL5, CCL18, TLR2, NLRP3, KLRD1, CTGF, and MMP9. Four hundred seventy children under the age of 10 years were included. Follicular trachoma (TF) was detected in 65 children (14%), C. trachomatis was detected in 25 (5%), and bacterial pathogens were cultured in 161 (34%). TF was associated with significantly increased expression of S100A7, IL17A, CCL18, CXCL5, and CTGF. Expression was increased further in the presence of papillary inflammation. Nonchlamydial bacterial infection was associated with increased expression of IL17A, CXCL5, CCL18, and KLRD1. IL17A expression was associated with increased expression of S100A7, CXCL5, CCL18, KLRD1, and CTGF. These data are consistent with a role for IL-17A in orchestrating the proinflammatory response in trachoma. Its activity may be promoted either as part of the cell-mediated response or through innate pathways. It may drive a range of proinflammatory factors leading to excessive tissue damage and repair involving fibrosis.

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“…For example, IL-22 can act in a synergistic manner with cytokines, such as IL-1a and tumor necrosis factor-a, to promote inflammation in the skin. 52 Furthermore, in bleomycin-induced airway inflammation, IL-22 has been reported to be pathogenic in the presence of IL-17A, but tissue protective in the absence of this cytokine. 53 With our finding of IL-17A being more highly expressed in the cecum than in the colon, it is possible that IL-17A expression may influence the outcome of IL-22 signaling in H. hepaticuseinduced disease.…”

Section: Th17 Cytokines In H Hepaticus Colitismentioning

confidence: 99%

Differential Requirements for IL-17A and IL-22 in Cecal versus Colonic Inflammation Induced by Helicobacter hepaticus

Morrison

Ballantyne

MacDonald

et al. 2015

The American Journal of Pathology

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Type 17 helper T-cell cytokines have been implicated in the pathogenesis of inflammatory bowel disease, a chronic condition affecting the gastrointestinal tract, but information regarding their contribution to pathology in different regions of the gut is lacking. By using a murine model of bacteria-induced typhlocolitis, we investigated the role of IL-17A, IL-17F, and IL-22 in cecal versus colonic inflammation. Cecal, but not colonic, pathology in C57BL/6 mice inoculated with Helicobacter hepaticus plus antieIL-10 receptor (IL-10R) monoclonal antibody was exacerbated by co-administration of antieIL-17A monoclonal antibody, suggesting a disease-protective role for IL-17A in the cecum. In contrast, antieIL-17F had no effect on H. hepaticus-induced intestinal pathology. Neutralization of IL-22 prevented the development of colonic, but not cecal, inflammation in H. hepaticus-infected antieIL-10Retreated mice, demonstrating a pathogenic role for IL-22 in the colon. Analysis of transcript levels revealed differential expression of IL-22R, IL-22 binding protein, and IL-23R between cecum and colon, a finding that may help explain why these tissues respond differently after antieIL-22 treatment. Analysis of microarray data from healthy human intestine further revealed significant differences in cytokine receptor transcript levels (including IL-22RA1 and IL-23R) in distinct parts of the human gut. Together, our findings demonstrate that individual type 17 helper T-cell cytokines can have proinflammatory or anti-inflammatory effects in different regions of the intestine, an observation that may have implications for interventions against human inflammatory bowel disease. (Am J Pathol 2015, 185: 3290e3303; http://dx

show abstract

Skin Inflammation Induced by the Synergistic Action of IL-17A, IL-22, Oncostatin M, IL-1α, and TNF-α Recapitulates Some Features of Psoriasis

Cited by 290 publications

References 49 publications

IL-37 Ameliorates the Inflammatory Process in Psoriasis by Suppressing Proinflammatory Cytokine Production

IL-37 Ameliorates the Inflammatory Process in Psoriasis by Suppressing Proinflammatory Cytokine Production

Active Trachoma Is Associated with Increased Conjunctival Expression ofIL17Aand Profibrotic Cytokines

Differential Requirements for IL-17A and IL-22 in Cecal versus Colonic Inflammation Induced by Helicobacter hepaticus

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