title: Deoxynivalenol as a new factor in the persistence of intestinal inflammatory diseases: an emerging hypothesis through possible modulation of Th17-mediated response.
abstract: OBJECTIVE
  Deoxynivalenol (DON) is a mycotoxin produced by Fusarium species which is commonly found in temperate regions worldwide as a natural contaminant of cereals. It is of great concern not only in terms of economic losses but also in terms of animal and public health. The digestive tract is the first and main target of this food contaminant and it represents a major site of immune tolerance. A finely tuned cross-talk between the innate and the adaptive immune systems ensures the homeostatic equilibrium between the mucosal immune system and commensal microorganisms. The aim of this study was to analyze the impact of DON on the intestinal immune response.
  
  
  METHODS
  Non-transformed intestinal porcine epithelial cells IPEC-1 and porcine jejunal explants were used to investigate the effect of DON on the intestinal immune response and the modulation of naive T cells differentiation. Transcriptomic proteomic and flow cytometry analysis were performed.
  
  
  RESULTS
  DON induced a pro-inflammatory response with a significant increase of expression of mRNA encoding for IL-8, IL-1α and IL-1β, TNF-α in all used models. Additionally, DON significantly induced the expression of genes involved in the differentiation of Th17 cells (STAT3, IL-17A, IL-6, IL-1β) at the expenses of the pathway of regulatory T cells (Treg) (FoxP3, RALDH1). DON also induced genes related to the pathogenic Th17 cells subset such as IL-23A, IL-22 and IL-21 and not genes related to the regulatory Th17 cells (rTh17) such as TGF-β and IL-10.
  
  
  CONCLUSIONS
  DON triggered multiple immune modulatory effects which could be associated with an increased susceptibility to intestinal inflammatory diseases.
authors: INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, Toulouse, France.
authors: Patricia M
authors: PM
authors: Cano
authors: Julie
authors: J
authors: Seeboth
authors: François
authors: F
authors: Meurens
authors: Juliette
authors: J
authors: Cognie
authors: Roberta
authors: R
authors: Abrami
authors: Isabelle P
authors: IP
authors: Oswald
authors: Laurence
authors: L
authors: Guzylack-Piriou
mesh_terms: D000818:Animals; D002460:Cell Line; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000473:pathology*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D023421:Models, Animal; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034421:Sus scrofa; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000378:metabolism; D014255:Trichothecenes / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D018925:Chemokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014255:Trichothecenes; C007262:deoxynivalenol