title: Intestinal irradiation and fibrosis in a Th1-deficient environment.
abstract: OBJECTIVE
  Changes in the Th1/Th2 immune balance may play a role in increasing the incidence of radiation-induced toxicity. This study evaluates the consequences of Th1 deficiency on intestinal response (fibrosis and T cell trafficking) to abdominal irradiation and examines in mucosa and mesenteric lymph nodes (MLN) the differential involvement of the two Th1 pathways, T-bet/STAT1 and IL-12/STAT4, in controlling this balance in mice.
  
  
  METHODS
  Using T-bet-deficient mice (T-bet-/-), we evaluated the mRNA and protein expression of the Th1 pathways (IFN-γ, T-bet/STAT1, and IL-12/STAT4) and the CD4+ and CD8+ populations in ileal mucosa and MLN during the first 3 months after 10 Gy abdominal irradiation.
  
  
  RESULTS
  The T-bet-deficient mice showed an increased fibrotic response to radiation, characterized by higher TGF-β1, col3a1 expression, and collagen deposition in mucosa compared with wild-type mice. This response was associated with drastically lower expression of IFN-γ, the hallmark Th1 cytokine. Analysis of the Th1 expression pathways, T-bet/STAT1 and IL-12/STAT4, showed their equal involvement in the failure of Th1 polarization. A minimal IFN-γ level depended on the IL-23-p19/STAT4 level. In addition, the radiation-induced deficiency in the priming of Th1 by IFN-γ was related to the defective homing capacity of CD8+ cells in the mucosa.
  
  
  CONCLUSIONS
  Irradiation induces Th2 polarization, and the Th2 immune response may play a role in potentiating irradiation-induced intestinal collagen deposition.
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France. christine.linard@irsn.fr
authors.forename: Christine
authors.initials: C
authors.lastname: Linard
authors.forename: Fabienne
authors.initials: F
authors.lastname: Billiard
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
mesh_terms: D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000528:radiation effects; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000528:radiation effects; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000528:radiation effects*; D024061:Collagen Type III / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism; D007082:Ileum / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000502:physiology; D053765:Interleukin-12 Subunit p35 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D053760:Interleukin-23 Subunit p19 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000172:deficiency* / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D018418:Th2 Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D024061:Collagen Type III; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D053760:Interleukin-23 Subunit p19; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D050797:STAT4 Transcription Factor; C494080:Stat1 protein, mouse; C494091:Stat4 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D053773:Transforming Growth Factor beta1; D018664:Interleukin-12; D007371:Interferon-gamma