Gut inflammation in mice triggers proliferation and function of mucosal foxp3(+) regulatory T cells but impairs their conversion from CD4(+) T cells

Abstract : Background and Aims: 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 naive 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.
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Submitted on : Monday, October 2, 2017 - 11:02:11 PM
Last modification on : Saturday, March 30, 2019 - 1:33:08 AM

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Gilles Boschetti, Reem Kanjarawi, Emilie Bardel, Sophie Collardeau-Frachon, Remi Duclaux-Loras, et al.. Gut inflammation in mice triggers proliferation and function of mucosal foxp3(+) regulatory T cells but impairs their conversion from CD4(+) T cells. Journal of Crohn's and Colitis, Elsevier - Oxford University Press, 2017, 11 (1), pp.105-117. ⟨10.1093/ecco-jcc/jjw125⟩. ⟨hal-01606706⟩

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