ArrayExpress Uploader064701Wild type Treg1Ebi3 –/– Treg1Ebi3 –/– Il10 –/– Treg1Il10 –/– Treg2Wild type Treg2Ebi3 –/– Treg2Il10 –/– Treg2Ebi3 –/– Il10 –/– Treg3Wild type Treg3Il10 –/– Treg3Ebi3 –/– Treg3Ebi3 –/– Il10 –/– Tregarrayexpress_sid6Regulatory T cells (Tregs) can suppress a wide variety of cell types, in diverse organ sites and inflammatory conditions. While Tregs...22013112E-GEOD-29262/profile/8773/arrayexpressuploader212cellinterleukininterleukin-10organDec.12, 2014Falsefunctional-plasticity-of-regulatory-t-cell-functioE-GEOD-29262_A-AFFY-45Functional Plasticity of Regulatory T Cell FunctionNov.11, 2014Regulatory T cells (Tregs) can suppress a wide variety of cell types, in diverse organ sites and inflammatory conditions. While Tregs possess multiple suppressive mechanisms, the number required for maximal function is unclear. Furthermore, whether any inter-relationship orcross-regulatory mechanisms exist that areused to orchestrate and control their utilization is unknown. Here we assessed the functional capacity of Tregs lacking the ability to secrete both interleukin-10 (IL-10) and IL-35, which individually are required for maximal Treg activity. Surprisingly, IL-10/IL-35-double deficient Tregswere fully functionalin vitro and in vivo. Loss of IL-10 and IL-35 was compensated for by a concurrent increase in cathepsin E (CTSE) expression, enhanced TRAIL (Tnfsf10)expression and soluble TRAIL release, rendering IL-10/IL-35-double deficient Tregsfunctionally dependent on TRAIL in vitro and in vivo. Lastly, while C57BL/6 Tregs are IL-10/IL-35-dependent, Balb/c Tregs, which express high levels of CTSE and enhanced TRAIL expression, are TRAIL-dependent.These data reveal that cross-regulatory pathways exist, which control the utilization of suppressive mechanisms,thereby providing Tregfunctional plasticity. Isolate natural Tregs from the different knockout mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-29262mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-29262/samples/