Association of the interleukin-22 genetic polymorphisms with ulcerative colitis

Chi, Hong Gang; Zheng, Xue; Wu, Zhu; Dai, Shi; Zheng, Weiping; Zou, Ying

doi:10.1186/s13000-014-0183-y

Cited by 10 publications

(10 citation statements)

References 41 publications

(39 reference statements)

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“…In patients with CD, this was associated with an increase in Th17, while depletion of Th22 cells was observed in UC patients (Leung and others 2014 ). So far, few studies have investigated IL22 polymorphisms in IBD susceptibility; however, since polymorphisms (rs1558744, rs7134599, rs2870946, and c.-429C/T) that are associated with increased UC risk have been identified in the IL22 gene locus, it is likely that deregulated IL-22 is also involved in CD pathogenesis (Silverberg and others 2009 ; Chi and others 2014 ).…”

Section: Activation Of Stat3 By the Il-10 Cytokine Family In Ibdmentioning

confidence: 99%

STAT3-Activating Cytokines: A Therapeutic Opportunity for Inflammatory Bowel Disease?

Nguyen

Putoczki

Ernst

2015

Journal of Interferon & Cytokine Research

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The gastrointestinal tract is lined by a single layer of epithelial cells that secrete mucus toward the lumen, which collectively separates the immune sentinels in the underlying lamina propria from the intestinal microflora to prevent aberrant immune responses. Inflammatory bowel disease (IBD) describes a group of autoimmune diseases that arise from defects in epithelial barrier function and, as a consequence, aberrant production of inflammatory cytokines. Among these, interleukin (IL)-6, IL-11, and IL-22 are elevated in human IBD patients and corresponding mouse models and, through activation of the JAK/STAT3 pathway, can both propagate and ameliorate disease. In particular, cytokine-mediated activation of STAT3 in the epithelial lining cells affords cellular protection, survival, and proliferation, thereby affording therapeutic opportunities for the prevention and treatment of colitis. In this review, we focus on recent insights gained from therapeutic modulation of the activities of IL-6, IL-11, and IL-22 in models of IBD and advocate a cautionary approach with these cytokines to minimize their tumor-promoting activities on neoplastic epithelium.

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Section: Activation Of Stat3 By the Il-10 Cytokine Family In Ibdmentioning

confidence: 99%

STAT3-Activating Cytokines: A Therapeutic Opportunity for Inflammatory Bowel Disease?

Nguyen

Putoczki

Ernst

2015

Journal of Interferon & Cytokine Research

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“…Positive association of il10rb polymorphisms with CD and UC particularly with early onset of IBD has been well documented [ 92 ]. In addition, the il22 gene is located within a UC-risk locus on chromosome 12q15 [ 93 ], and il22 polymorphism in UC patients has been reported in the Chinese [ 94 ], but not Mexican [ 95 ], population. The ligation of IL-22 receptor is well known to induce the activation of STAT3 through JAK2 and TYK2.…”

Section: Introductionmentioning

confidence: 99%

Clinical importance of IL-22 cascade in IBD

et al. 2017

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IL-22 is a relatively new cytokine that is characterized by several unique biological properties. In the intestines, the effect of IL-22 is restricted mainly to non-lymphoid cells such as epithelial cells. Interestingly, the expression pattern and major cellular source of IL-22 have distinct difference between large and small intestines. IL-22 possesses an ability to constitutively activate STAT3 for promoting epithelial cell regeneration and reinforcing mucosal barrier integrity through stimulating the expression of anti-bacterial peptide and mucins. Of note, IL-22 is characterized as a two-faced cytokine that can play not only protective but also deleterious roles in the intestinal inflammation depending on the cytokine environment such as the expression levels of IL-23, T-bet, and IL-22 binding protein. Most importantly, clinical relevance of IL-22 to inflammatory bowel disease has been well highlighted. Mucosal healing, which represents the current therapeutic goal for IBD, can be induced by IL-22. Indeed, indigo naturalis, which can activate IL-22 pathway through Ahr, has been shown in a clinical trial to exhibit a strong therapeutic effect on ulcerative colitis. Despite the beneficial effect of IL-22, continuous activation of the IL-22 pathway increases the risk of colitis-associated cancer, particularly in patients with an extended history of IBD. This review article discusses how IL-22 regulates colitis, how beneficial versus deleterious effects of IL-22 is determined, and why IL-22 represents a promising target for IBD therapy.

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“…As already alluded to, butyrate [10,11] and IL-22 [32] are regarded protective factors in ulcerative colitis. Interestingly, recent data also propose relevance of an IL-22 polymorphism (429C/T) for ulcerative colitis pathogenesis [46].…”

Section: Discussionmentioning

confidence: 99%

Cooperation between the bacterial‐derived short‐chain fatty acid butyrate and interleukin‐22 detected in human Caco2 colon epithelial/carcinoma cells

et al. 2016

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By generating biologically active factors luminal microbiota shape the intestinal micro-milieu thereby regulating pathological processes such as inflammation and carcinogenesis. Preclinical data suggest that bacterial-derived butyrate and the signal transducer and activator of transcription (STAT)-3 activating cytokine interleukin (IL)-22 display concordant protective properties at the inflamed colonic epithelium. Herein, biochemical cooperation between the short-chain fatty acid butyrate and IL-22 was investigated by focusing on human Caco2 colon epithelial/carcinoma cells. We report that physiological levels of butyrate enhance IL-22 signaling thereby enforcing expression of the prototypic STAT3-downstrean target genes α1-antichymotrypsin and suppressor of cytokine signaling (SOCS)-3. A dual mode of butyrate action on the IL-22/STAT3 axis was identified. Butyrate acted by upregulating IL-22R1, the decisive chain of the heterodimeric IL-22 receptor, and, independent from that, has the potential to directly amplify STAT3-mediated gene activation as detected by chromatin immunoprecipitation analysis of STAT3 binding to the SOCS3 promoter. Since trichostatin A acted similarly, inhibition of histone deacetylases is likely at the root of these butyrate biological properties. The mutual benefit gained from interactions between the host and commensal intestinal bacteria-derived factors is an expanding field of research beginning to affect clinical practice. Data presented herein propose a supportive and fine-tuning role for butyrate in IL-22 signaling that might be therapeutically exploited by local butyrate administration or by increasing its bacterial production in the context of a fiber-rich diet. © 2016 BioFactors, 43(2):283-292, 2017.

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Association of the interleukin-22 genetic polymorphisms with ulcerative colitis

Cited by 10 publications

References 41 publications

STAT3-Activating Cytokines: A Therapeutic Opportunity for Inflammatory Bowel Disease?

STAT3-Activating Cytokines: A Therapeutic Opportunity for Inflammatory Bowel Disease?

Clinical importance of IL-22 cascade in IBD

Cooperation between the bacterial‐derived short‐chain fatty acid butyrate and interleukin‐22 detected in human Caco2 colon epithelial/carcinoma cells

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