Research Paper Volume 8, Issue 6 pp 1223—1235

Figure 7. Flow chart representation of the main conclusions of the paper. RA present in the mucosa in known to induce tolerance via induction of T regs. However, the mechanisms of T reg induction are not understood. Here we outline a novel mechanism of induction of T regs by RA which is impaired in the elderly. Exposure of young DCs to RA induces the upregulation of expression of CD141 and GARP/LRRC32 on DCs. The culture of CD141hi GARP+ DCs with CD4 T cells leads to the induction of T regulatory cells and IL-10 secretion versus the CD141lo GARP− DCs. This suggests that RA induces T regs via CD141 and GARP expression which maintains mucosal tolerance and prevents inflammation. In contrast to young, DCs from aged subjects are impaired in their capacity to upregulate CD141 and GARP after treatment with RA. This reduces their capacity to induce T regs and maintain mucosal tolerance and control inflammation.