Genome-wide expression profiling during protection from colitis by regulatory T cells

Kristensen, Nanna Ny; Olsen, Jørgen; Gad, Monika; Claësson, Mogens H.

doi:10.1002/ibd.20277

Cited by 16 publications

(16 citation statements)

References 68 publications

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“…Although known primarily as a CCR5 antagonist, TAK-779 has also been shown to block CXCR3 in mice, but not in humans 49–51 . Although CXCR3 expression has been described on Treg in some models of inflammation 62,63 , we did not observe expression of CXCR3 on Treg in our tumor-bearing mice (data not shown). Another compound, Met-CCL5, is a CCR1 and CCR5 antagonist 64 , which has been shown to inhibit the growth of murine breast carcinoma in vivo ; however, in this tumor model, there is little CD4 + lymphocytic infiltration 65 .…”

Section: Discussioncontrasting

confidence: 63%

Disruption of CCR5-Dependent Homing of Regulatory T Cells Inhibits Tumor Growth in a Murine Model of Pancreatic Cancer

Tan

Goedegebuure

Belt³

et al. 2009

The Journal of Immunology

384

333

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Tumors evade immune destruction by actively inducing immune tolerance through the recruitment of CD4+CD25+Foxp3+ regulatory T cells (Treg). We have previously described increased prevalence of these cells in pancreatic adenocarcinoma, but it remains unclear what mechanisms are involved in recruiting Treg into the tumor microenvironment. Here, we postulated that chemokines might direct Treg homing to tumor. We show, in both human pancreatic adenocarcinoma and a murine pancreatic tumor model (Pan02), that tumor cells produce increased levels of ligands for the CCR5 chemokine receptor, and, reciprocally, that CD4+ Foxp3+ Treg, compared with CD4+ Foxp3− effector T cells, preferentially express CCR5. When CCR5/CCL5 signaling is disrupted, either by reducing CCL5 production by tumor cells or by systemic administration of a CCR5 inhibitor (TAK-779), Treg migration to tumors is reduced and tumors are smaller than in control mice. Thus, this study demonstrates the importance of Treg in immune evasion by tumors, how blockade of Treg migration may inhibit tumor growth, and, specifically in pancreatic adenocarcinoma, the role of CCR5 in the homing of tumor-associated Treg. Selective targeting of CCR5/CCL5 signaling may represent a novel immunomodulatory strategy for the treatment of cancer.

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Section: Discussioncontrasting

confidence: 63%

Disruption of CCR5-Dependent Homing of Regulatory T Cells Inhibits Tumor Growth in a Murine Model of Pancreatic Cancer

Tan

Goedegebuure

Belt³

et al. 2009

The Journal of Immunology

384

333

View full text Add to dashboard Cite

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“…4). This is in agreement with a previous study where we found the expression of cxcl5 to be upregulated more than 50-fold in colitic animals, 23 thus indicating that this chemokine does play a very important role in induction and maintenance of colitis. The cytokine CXCL5 released by intestinal epithelial cells is known to recruit CXCR2-expressing neutrophils to the site of inflammation both in mouse and man.…”

Section: Discussionsupporting

confidence: 94%

Consumption of probiotics increases the effect of regulatory T cells in transfer colitis

Petersen¹,

Claësson²,

Schmidt³

et al. 2012

Inflammatory Bowel Diseases

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“…These data reveal that the majority of differentially expressed genes during both DSS colitis and UC are upregulated, while a lesser number are downregulated. Interestingly, these data identify a greater number of similarly regulated genes than previously reported (41,29).…”

Section: Genome Profiling Of Experimental and Ulcerative Colitismentioning

confidence: 62%

Temporal genomewide expression profiling of DSS colitis reveals novel inflammatory and angiogenesis genes similar to ulcerative colitis

Fang

Bruce

Pattillo

et al. 2011

Physiological Genomics

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Dextran sodium sulfate (DSS)-induced colitis is widely used to study pathological mechanisms and potential treatments of inflammatory bowel disease. Because temporal changes in genome expression profiles remain unknown in this model, we performed whole genome expression profile analysis during the development of DSS colitis in comparison with ulcerative colitis (UC) specimens to identify novel and common responses during disease. Colon tissue from DSS-treated mice was collected at days 0, 2, 4, and 6. Half of each specimen was used for histopathological analysis and half for Affymetrix whole genome expression profiling and qRT-PCR validation. Genesifter and Ingenuity software analysis was used to identify differentially expressed genes and perform interactive network analysis. Identified DSS-associated genes in mice were also compared with UC patient data. We identified 1,609 genes that were significantly altered during DSS colitis; the majority were functionally related to inflammation, angiogenesis, metabolism, biological adhesion, cellular growth and proliferation, and cell-to-cell signaling responses. Five hundred and one genes were progressively upregulated, while one hundred seventy-three genes were progressively downregulated. Changes in gene expression were validated in a subset of 33 genes by qRT-PCR, with r(2) = 0.925. Ingenuity gene interaction network analysis revealed novel relationships among antigen presentation, cell morphology, and other biological functions in the DSS mouse. Finally, DSS colitis gene array data were compared with UC patient array data: 152 genes were similarly upregulated, and 22 genes were downregulated. Temporal genomewide expression profile analysis of DSS-induced colitis revealed novel associations with various immune responses and tissue remodeling events such as angiogenesis similar to those in UC patients. This study provides a comprehensive view of DSS colitis changes in colon gene expression and identifies common molecules with clinical specimens that are interesting targets for further investigation.

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Genome-wide expression profiling during protection from colitis by regulatory T cells

Abstract: We suggest that these molecules alone or in combination could be future therapeutic targets.

Cited by 16 publications

References 68 publications

Disruption of CCR5-Dependent Homing of Regulatory T Cells Inhibits Tumor Growth in a Murine Model of Pancreatic Cancer

Disruption of CCR5-Dependent Homing of Regulatory T Cells Inhibits Tumor Growth in a Murine Model of Pancreatic Cancer

Consumption of probiotics increases the effect of regulatory T cells in transfer colitis

Temporal genomewide expression profiling of DSS colitis reveals novel inflammatory and angiogenesis genes similar to ulcerative colitis

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