Interleukin-22, a Member of the IL-10 Subfamily, Induces Inflammatory Responses in Colonic Subepithelial Myofibroblasts

Andoh, Akira; Zhang, Zhuobin; Inatomi, Osamu; Fujino, Sanae; Deguchi, Yasuyuki; Araki, Yoshio; Tsujikawa, Tomoyuki; Kitoh, Katsuyuki; Kim‐Mitsuyama, Shokei; Takayanagi, Atsushi; Shimizu, Nobuyoshi; Fujiyama, Yoshihide

doi:10.1053/j.gastro.2005.06.071

Cited by 435 publications

(390 citation statements)

References 43 publications

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“…The coexpression of IL-22 with IL-17A and IL-17F by Th17 cells suggests that these cytokines may function together to modulate inflammation. IL-22 can function in synergy with IL-17A or IL-17F on human colonic myofibroblasts and/or human keratinocytes to induce proinflammatory mediators (17,29).…”

mentioning

confidence: 99%

An IL-17F/A Heterodimer Protein Is Produced by Mouse Th17 Cells and Induces Airway Neutrophil Recruitment

Liang

Long²,

Bennett³

et al. 2007

The Journal of Immunology

311

252

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IL-17A and IL-17F are related homodimeric proteins of the IL-17 family produced by Th17 cells. In this study, we show that mouse Th17 cells also produce an IL-17F/A heterodimeric protein. Whereas naive CD4+ T cells differentiating toward the Th17 cell lineage expressed IL-17F/A in higher amounts than IL-17A/A homodimer and in lower amounts than IL-17F/F homodimer, differentiated Th17 cells expressed IL-17F/A in higher amounts than either homodimer. In vitro, IL-17F/A was more potent than IL-17F/F and less potent than IL-17A/A in regulating CXCL1 expression. Neutralization of IL-17F/A with an IL-17A-specific Ab, and not with an IL-17F-specific Ab, reduced the majority of IL-17F/A-induced CXCL1 expression. To study these cytokines in vivo, we established a Th17 cell adoptive transfer model characterized by increased neutrophilia in the airways. An IL-17A-specific Ab completely prevented Th17 cell-induced neutrophilia and CXCL5 expression, whereas Abs specific for IL-17F or IL-22, a cytokine also produced by Th17 cells, had no effects. Direct administration of mouse IL-17A/A or IL-17F/A, and not IL-17F/F or IL-22, into the airways significantly increased neutrophil and chemokine expression. Taken together, our data elucidate the regulation of IL-17F/A heterodimer expression by Th17 cells and demonstrate an in vivo function for this cytokine in airway neutrophilia.

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confidence: 99%

An IL-17F/A Heterodimer Protein Is Produced by Mouse Th17 Cells and Induces Airway Neutrophil Recruitment

Liang

Long²,

Bennett³

et al. 2007

The Journal of Immunology

311

252

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“…Recently, it was suggested that IL-22 has a central role in the pathophysiology of inflammatory bowel disease. 21,22 REG Ia, on the other hand, has been isolated in several microarray studies as a distinctly upregulated gene in the colonic epithelium in ulcerative colitis (UC). 23,24 Interestingly, Zheng et al 14 have recently reported that IL-22 mediates host defense against bacterial pathogens by inducing Reg family proteins in mice.…”

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confidence: 99%

Involvement of the IL-22/REG Iα axis in ulcerative colitis

Sekikawa

Fukui

Suzuki

et al. 2010

Laboratory Investigation

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The Regenerating gene (REG) Ia protein, a trophic and/or anti-apoptotic factor, is important in the pathophysiology of gastrointestinal inflammation. Interleukin (IL)-22 is a recently identified cytokine that is suggested to have pivotal roles in inflammatory bowel diseases. We therefore investigated the involvement of the IL-22/REG Ia axis and examined the mechanism of regulation of REG Ia expression by IL-22 stimulation in ulcerative colitis (UC) mucosa. Expression of IL-22, IL-22 receptor 1 (IL-22R1), and REG Ia in UC mucosa was analyzed by real-time RT-PCR and immunohistochemistry. The effects of IL-22 on REG Ia protein expression were examined using a small-interfering RNA for STAT3, an MAPK inhibitor or a PI3K inhibitor. The element responsible for IL-22-induced REG Ia promoter activation was determined by a promoter deletion and electrophoretic mobility shift assay. The expression of IL-22 was enhanced in infiltrating inflammatory cells, and that of IL-22R1 and REG Ia was concurrently enhanced in the inflamed epithelium in UC mucosa. The levels of REG Ia and IL-22 mRNA expression were strongly correlated, and the distributions of REG Ia-and IL-22R1-positive epithelial cells were very similar. IL-22 simulation enhanced the expression of REG Ia protein through STAT3 tyrosine phosphorylation in colon cancer cells. The IL-22-responsive element was located between À142 and À134 in the REG Ia promoter region. REG Ia protein may have a pathophysiological role as a biological mediator for immune cell-derived IL-22 in the UC mucosa.

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“…[1][2][3][4] IL-19, IL-20, IL-22, IL-24, and IL-26 share structural characteristics and make up the IL-20 subfamily. Although IL-10 is immunosuppressive in the immune system, IL-20 subfamily cytokines are likely to be proinflammatory.…”

mentioning

confidence: 99%

“…Although IL-10 is immunosuppressive in the immune system, IL-20 subfamily cytokines are likely to be proinflammatory. 2,5,6 In monocytes IL-19 secretion in response to LPS and GM-CSF has been shown to induce monocyte production of proinflammatory cytokines. 7 IL-19 expression is also upregulated in psoriatic lesions, [8][9][10] in sera from asthmatic patients, and in the urine of uremic patients, although the source of IL-19 production has not yet been identified.…”

mentioning

confidence: 99%

Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma

Huang

Wachi

Thai

et al. 2008

Journal of Allergy and Clinical Immunology

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Interleukin-22, a Member of the IL-10 Subfamily, Induces Inflammatory Responses in Colonic Subepithelial Myofibroblasts

Cited by 435 publications

References 43 publications

An IL-17F/A Heterodimer Protein Is Produced by Mouse Th17 Cells and Induces Airway Neutrophil Recruitment

An IL-17F/A Heterodimer Protein Is Produced by Mouse Th17 Cells and Induces Airway Neutrophil Recruitment

Involvement of the IL-22/REG Iα axis in ulcerative colitis

Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: Important implications in asthma

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