title: The retinoic acid receptor agonist Am80 increases mucosal inflammation in an IL-6 dependent manner during Trichuris muris infection.
abstract: OBJECTIVE
  Vitamin A metabolites, such as all-trans-retinoic acid (RA) that act through the nuclear receptor; retinoic acid receptor (RAR), have been shown to polarise T cells towards Th2, and to be important in resistance to helminth infections. Co-incidentally, people harbouring intestinal parasites are often supplemented with vitamin A, as both vitamin A deficiency and parasite infections often occur in the same regions of the globe. However, the impact of vitamin A supplementation on gut inflammation caused by intestinal parasites is not yet completely understood.
  
  
  METHODS
  Here, we use Trichuris muris, a helminth parasite that buries into the large intestine of mice causing mucosal inflammation, as a model of both human trichuriasis and IBD, treat with an RARα/β agonist (Am80) and quantify the ensuing pathological changes in the gut.
  
  
  RESULTS
  Critically, we show, for the first time, that rather than playing an anti-inflammatory role, Am80 actually exacerbates helminth-driven inflammation, demonstrated by an increased colonic crypt length and a significant CD4(+) T cell infiltrate. Further, we established that the Am80-driven crypt hyperplasia and CD4(+) T cell infiltrate were dependent on IL-6, as both were absent in Am80-treated IL-6 knock-out mice.
  
  
  CONCLUSIONS
  This study presents novel data showing a pro-inflammatory role of RAR ligands in T. muris infection, and implies an undesirable effect for the administration of vitamin A during chronic helminth infection.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK, rebecca.hurst@manchester.ac.uk.
authors.forename: Rebecca J M
authors.initials: RJ
authors.lastname: Hurst
authors.forename: Adam
authors.initials: A
authors.lastname: De Caul
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Little
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kagechika
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Else
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D002908:Chronic Disease; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000494:pharmacology*; D015850:Interleukin-6 / Q000172:deficiency / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018168:Receptors, Retinoic Acid / Q000819:agonists; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014257:Trichuriasis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D014258:Trichuris / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D001565:Benzoates; D018836:Inflammation Mediators; D015850:Interleukin-6; D018168:Receptors, Retinoic Acid; D013764:Tetrahydronaphthalenes; C061133:tamibarotene
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