title: Gut Inflammation in Mice Triggers Proliferation and Function of Mucosal Foxp3+ Regulatory T Cells but Impairs Their Conversion from CD4+ T Cells.
abstract: OBJECTIVE
  Regulatory Foxp3+CD4+T cells [Tregs] have been implicated in the control of colitis in T-cell transfer models, yet their ability to regulate colitis induced by innate immunity and the impact of gut inflammation on their fate and function have been poorly documented.
  
  
  METHODS
  Colitis was induced by dextran sodium sulphate in DEREG transgenic mice. Tregs ablation and transfer experiments showd that Tregs could limit the severity of colitis in B6 mice.
  
  
  RESULTS
  Gut inflammation resulted in increased number of Tregs in mesenteric lymph nodes [MLN] and colon lamina propria [LP], although their frequency decreased due to massive concomitant leukocyte infiltration. This coincided at both sites with a dramatic increase in Ki67+Tregs which retained proliferative capacity. Gut inflammation resulted in enhanced suppressive function of Tregs in colon lamina propria and neuropillin-1-[NRP1-] Treg in MLN. Real-time polymerase chain reaction analysis and flow cytometry [using IL10-egfp-reporter mice] showed that compared with NRP1+Treg, NRP1-Treg express higher levels of IL-10 transcripts and were enriched in IL10-expressing cells both in the steady state and during colitis. Moreover, Treg conversion in vivo from from naïve CD4+T cells or Treg precursors was impaired in colitic mice. Finally, gut inflammation caused a decrease in intestinal dendritic cells, affecting both CD103+CD11b+and CD103+CD11b-subsets and affected their Treg conversion capacity.
  
  
  CONCLUSIONS
  Together, our data indicate that non-specific colon inflammation triggers proliferation and suppressive function of Tregs in the lamina propria and MLN, but impairs their de novo conversion from CD4+T cells by intestinal dendritic cells.
authors.forename: Gilles
authors.initials: G
authors.lastname: Boschetti
authors.forename: Reem
authors.initials: R
authors.lastname: Kanjarawi
authors.forename: Emilie
authors.initials: E
authors.lastname: Bardel
authors.affiliation: Hospices Civils de Lyon, Department of Pathology, Hôpital Femme-Mere-Enfant, Lyon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Collardeau-Frachon
authors.forename: Remi
authors.initials: R
authors.lastname: Duclaux-Loras
authors.forename: Ludovic
authors.initials: L
authors.lastname: Moro-Sibilot
authors.forename: Thibaut
authors.initials: T
authors.lastname: Almeras
authors.forename: Bernard
authors.initials: B
authors.lastname: Flourié
authors.forename: Stephane
authors.initials: S
authors.lastname: Nancey
authors.forename: Dominique
authors.initials: D
authors.lastname: Kaiserlian
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D003092:Colitis / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology / Q000503:physiopathology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse
keywords: Colitis; Treg; dendritic cells; function; mice