S Kyle Pauly, John H Fechner, Xiaoji Zhang, Jose Torrealba, Christopher A Bradfield, Joshua D Mezrich
{"title":"The Aryl Hydrocarbon Receptor Influences Transplant Outcomes in Response to Environmental Signals.","authors":"S Kyle Pauly, John H Fechner, Xiaoji Zhang, Jose Torrealba, Christopher A Bradfield, Joshua D Mezrich","doi":"10.1080/02772248.2012.688546","DOIUrl":null,"url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AHR) is a cytosolic transcription factor with numerous endogenous and xenobiotic ligands, most notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Recent data suggests that TCDD may induce regulatory T cells, while a second AHR ligand, FICZ, promotes Th17 differentiation. The aim was to examine whether injection of recipient mice with either TCDD or FICZ altered skin allograft rejection in a fully mismatched model. TCDD or FICZ was given to recipient C57BL/6 mice intraperitoneally (IP). Twenty-four hr later, donor skin was grafted from BALB/c mice. An additional dose of FICZ was given on day 3. Treatment with TCDD delayed graft rejection for more than 4 weeks while FICZ treatment accelerated rejection by 1 - 2 days. In vivo exposure with TCDD led to a rise in the frequency of FoxP3(+) CD4(+) T cells in the spleen, while FICZ increased IL-17 secretion by splenocytes from treated animals. Activation of the AHR receptor by different AHR ligands in vivo resulted in opposing effects on skin graft survival. AHR serves as a sensor to environmental signals, with effects on the acquired immune system that may alter outcomes after organ transplantation. This model will be useful to further delineate direct effects of the environment on the immune system and outcomes of organ transplantation.</p>","PeriodicalId":23122,"journal":{"name":"Toxicological and Environmental Chemistry","volume":"94 6","pages":"1175-1187"},"PeriodicalIF":1.1000,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/02772248.2012.688546","citationCount":"18","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicological and Environmental Chemistry","FirstCategoryId":"93","ListUrlMain":"https://doi.org/10.1080/02772248.2012.688546","RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2012/6/20 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
引用次数: 18
Abstract
The aryl hydrocarbon receptor (AHR) is a cytosolic transcription factor with numerous endogenous and xenobiotic ligands, most notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Recent data suggests that TCDD may induce regulatory T cells, while a second AHR ligand, FICZ, promotes Th17 differentiation. The aim was to examine whether injection of recipient mice with either TCDD or FICZ altered skin allograft rejection in a fully mismatched model. TCDD or FICZ was given to recipient C57BL/6 mice intraperitoneally (IP). Twenty-four hr later, donor skin was grafted from BALB/c mice. An additional dose of FICZ was given on day 3. Treatment with TCDD delayed graft rejection for more than 4 weeks while FICZ treatment accelerated rejection by 1 - 2 days. In vivo exposure with TCDD led to a rise in the frequency of FoxP3(+) CD4(+) T cells in the spleen, while FICZ increased IL-17 secretion by splenocytes from treated animals. Activation of the AHR receptor by different AHR ligands in vivo resulted in opposing effects on skin graft survival. AHR serves as a sensor to environmental signals, with effects on the acquired immune system that may alter outcomes after organ transplantation. This model will be useful to further delineate direct effects of the environment on the immune system and outcomes of organ transplantation.
期刊介绍:
The journal is interdisciplinary in outlook, and manuscripts published in it cover all relevant areas: • inorganic chemistry – trace elements in food and the environment, metal complexes and chelates; • organic chemistry – environmental fate, chemical reactions, metabolites and secondary products, synthesis of standards and labelled materials; • physical chemistry – photochemistry, radiochemistry; • environmental chemistry – sources, fate, and sinks of xenochemicals, environmental partitioning and transport, degradation and deposition; • analytical chemistry – development and optimisation of analytical methods, instrumental and methodological advances, miniaturisation and automation; • biological chemistry – pharmacology and toxicology, uptake, metabolism, disposition of xenochemicals, structure-activity relationships, modes of action, ecotoxicological testing.