Gut Inflammation in Mice Triggers Proliferation and Function of Mucosal Foxp3+ Regulatory T Cells but Impairs Their Conversion from CD4+ T Cells.

Background And Aims: Regulatory Foxp3CD4 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 CD103CD11b and CD103CD11b 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.