IL-22 Induces an Acute-Phase Response

Liang, Spencer; Nickerson‐Nutter, Cheryl; Pittman, Debra D.; Carrier, Yijun; Goodwin, Debra G.; Shields, Kathleen; Lambert, Andre-Jean; Schelling, Scott H.; Medley, Quintus G.; Ma, Huiyuan; Collins, Mary; Dunussi‐Joannopoulos, Kyriaki; Fouser, Lynette A.

doi:10.4049/jimmunol.0904091

Cited by 169 publications

(153 citation statements)

References 49 publications

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“…The exact mechanism of how IL-22 works as a pro-inflammatory cytokine in an LPS-induced ALI model remains to be determined. Interestingly, a previous report suggested that the systemic injection of IL-22 alone can cause most of the acute phase responses (38). In a psoriasis model, IL-22 KO mice showed less neutrophil accumulation (37).…”

Section: Discussionmentioning

confidence: 99%

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Innate-like function of memory Th17 cells for enhancing endotoxin-induced acute lung inflammation through IL-22

Sakaguchi

Chikuma

Shichita

et al. 2015

International Immunology

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Section: Discussionmentioning

confidence: 99%

“…In these models, IL-22 has been shown to induce chemokines (CXCL1 and CXCL5), as well as inflammatory gene expression, from target tissue (i.e. lung or skin) (17,38,39). It was also proposed that serum amyloid A, induced by IL-22, may promote the downstream pathway of inflammation (38).…”

Section: Discussionmentioning

confidence: 99%

Innate-like function of memory Th17 cells for enhancing endotoxin-induced acute lung inflammation through IL-22

Sakaguchi

Chikuma

Shichita

et al. 2015

International Immunology

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“…[40][41][42][43] Our study reveals IL-22, secreted by leukocytes infiltrating WAT of obese animals, and its receptor IL-22R, expressed by tumor cells, as a candidate pathway upstream of CXCL1 activation in cancer (Fig. 2).…”

Section: Infiltration Of Wat By Il-22-expressing Leukocytes and Il-22mentioning

confidence: 99%

“…39 In that study, multiplex analysis of mouse plasma identified IL-22 as the only cytokine (in the panel of 50 cytokines) circulation of which in peripheral blood was dramatically (50 times) higher in obese tumor-bearing mice compared to lean tumor-bearing mice. Because IL-22 signaling through the IL-22 receptor (IL-22R) has been previously identified as a pathway inducing the expression of CXCL1 in the epithelium, [40][41][42][43] we set out to test if the pattern of IL-22 / IL-22R expression is consistent with its potential role in obesity-associated CXCL1 induction. Figure 1.…”

Section: Systemic Circulation Of Il-22 Is Increased In Obesitymentioning

confidence: 99%

Cytokine signaling regulating adipose stromal cell trafficking

Zhang

Kolonin

2016

Adipocyte

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Adipocyte progenitors, known as adipose stromal cells (ASC), can become mobilized, recruited by tumors, and contribute to cancer progression. Mechanisms underlying ASC trafficking have remained obscure. We recently reported that CXCL1 expressed by cancer cells chemoattracts ASC expressing CXCR1 in obesity. As a candidate mechanism of CXCL1 activation, we identified interleukin (IL)-22, systemic circulation of which is increased in obesity. It has been reported that IL-22 signaling through IL-22R is upstream of CXCL1. Here, we provide evidence that IL-22 expression by leukocytes infiltrating WAT and IL-22R expression by tumors is obesity-dependent. We propose that obesity-associated adipocyte death and the resulting recruitment of leukocytes triggers the IL-22 signaling cascade that induces CXCL1 secretion by cancer cells responsible for ASC trafficking to tumors. KEYWORDS adipose stromal cell; cytokine; chemokine; CXCL1; cancer; interleukin-22; receptor; obesity Epidemiology studies have indicated that progression of many cancers is associated with obesity. 1-5 Excess white adipose tissue (WAT) directly contributes to disease progression, alongside with obesity-associated lifestyle and diet. 6,7 Our studies using mouse models have shown that excess of WAT, which is overgrown in obese individuals, promotes tumor growth irrespective of diet used to induce obesity. 8,9 WAT is composed by adipocytes and vascular/stromal cells. 10,11 Adipose stromal cells (ASC) serve as the mesenchymal progenitors of adipocytes and as endothelium-supporting perivascular cells 12-14 with potent angiogenic capacity. 15 While malignant cells with ASC properties comprise an integral component of liposarcomas, tumors derived from WAT, 16 it is benign ASC that promote carcinoma progression. Along with other WAT cells, ASC secrete hormones, inflammatory cytokines, and growth factors collectively termed adipokines, many of which have pro-tumorigenic properties. 17,18 It has been discovered that, like bone marrow mesenchymal stem cells (MSC), 19 ASC can become mobilized and traffic outside WAT. [20][21][22] Because numbers of ASC increase in obesity, we had hypothesized that WAT is a contributor to the pool of tumor stromal cells. 23,24 We have identified ASC trafficking to tumors as the mechanism underlying the obesity-cancer link. In animal studies, administered ASC engraft tumors, which results in accelerated cancer progression. 8,9,[25][26][27] Our findings confirmed by data from other laboratories demonstrate tumor homing of endogenous ASC in obesity, which is concomitant with increased vascularization and adipogenesis promoting survival and proliferation of neighboring malignant cells. [28][29][30][31][32] The apparent contribution of ASC to the tumor stroma has raised a question regarding the safety of lipotransfer procedures in cancer patients. 33,34 Specific molecular mechanisms through which ASC promote cancer are being investigated, and it is becoming apparent that paracrine factors secreted by ASC within the tumor larg...

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“…14 Although its major activities occur locally, IL-22 can be detected in the circulation and it stimulates hepatocytes to synthesize acute phase reactants in acute inflammatory conditions. 15 IL-22 has multiple effects on epithelial cells. Although the details vary from tissue to tissue, these effects can be grouped into three broad categories 3,4 : (1) strengthening resistance to pathogens by stimulating the generation of antimicrobial proteins (including defensins, S100A family proteins, neutrophil gelatinase-associated lipocalin, and lipocalin) and through the release of selected chemokines; (2) protecting against cell death by increasing expression of antiapoptotic proteins (Bcl2) and decreasing expression of proapoptotic proteins (Bax and Bad); and (3) promoting repair by increasing epithelial cell proliferation and inhibiting terminal differentiation.…”

mentioning

confidence: 99%

All of the Twos, 22—Bingo!

Rees

2014

Journal of the American Society of Nephrology

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is critical in embryogenesis, whereas BMP7 is critical in kidney development regulating the differentiation of metanephric mesenchymal cells required for ureteric bud branching. [11][12][13] It is tempting to speculate that BMP7 regulation of Tet3 expression and the resulting effect on the epigenome play an important role in nephrogenesis.The study by Tampe et al. 7 indicates that Rasal1 promoter hypermethylation and reduced Tet3 expression are features of renal fibrosis. BMP7 treatment resulted in normalization of Tet3 expression and consequently hydroxymethylation of the Rasal1 promoter. BMP7-mediated hydroxymethylation of the Rasal1 promoter was impaired when Tet3 expression was lost. Electrophoretic mobility shift assays confirmed binding of Tet3 to its CXXC binding motif flanking the Rasal1 CpG island promoter, further indicating the role of Tet3 in Rasal1 hydroxymethylation.Preclinical data from this study indicate that aberrant methylation or perhaps active demethylation processes catalyzed by Tet3 determine the balance between health and CKD. These findings suggest that transient therapies targeted at amplifying or restoring Tet3 activity may prove beneficial to patients with CKD. Furthermore, analysis of methylation status (e.g., using RASAL1 as a methylation biomarker) to determine the individual risk of a patient to develop fibrosis or suitability for demethylation-based therapy appears both plausible and attractive. However, further studies in larger patient cohorts are warranted to establish these targets for both diagnosis and therapy.Demethylation agents, such as 5-azacytidine, have already been described to rescue kidney fibrosis in experimental models 3 and demethylation agents are in clinical trials for treatment of cancers; however, these drugs are cytotoxic and the long-term effects of genome-wide demethylation are unknown. It therefore seems more attractive to transiently and specifically reactivate an endogenous demethylation process and thereby readdress the imbalance that results in CKD. The identification of Tet3 as a critical player in both the development and reversal of renal fibrogenesis described in the study by Tampe et al. 7 may be the first step toward achieving this attractive possibility.

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IL-22 Induces an Acute-Phase Response

Cited by 169 publications

References 49 publications

Innate-like function of memory Th17 cells for enhancing endotoxin-induced acute lung inflammation through IL-22

Innate-like function of memory Th17 cells for enhancing endotoxin-induced acute lung inflammation through IL-22

Cytokine signaling regulating adipose stromal cell trafficking

All of the Twos, 22—Bingo!

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