page 1051. Annacker and colleagues show that DCs expressing the integrin CD103 are required for T reg cells to subdue gut-attacking effector T cells in a mouse model of inflammatory bowel disease (IBD).Naturally occurring T reg cells help protect against autoimmunity and excessive inflammation by suppressing the activity of effector T cells. This group had previously shown that transferring T reg cells protects against T cell–induced IBD in mice. The suppression of IBD requires the cytokine TGF-β and possibly the high levels of CD103 that are seen in a subset of T reg cells.
Annacker et al. now show, however, that CD103 is not required on the effector T cells for them to induce disease, nor on the T reg cells for them to suppress disease. However, CD103 was not completely expendable. T reg cells could not suppress colitis when transferred into CD103-deficient mice, suggesting that CD103 expression on non–T cells somehow spurs the T reg cells into action.
The relevant CD103-expressing cells were DCs, consistent with the study by Johansson-Lindbom et al. (page 1063) showing that CD103 marks lymph node DCs that originated in the gut. But how these DCs communicate with T reg cells is not clear. Both groups showed that CD103+ DCs, but not CD103− DCs, induced the expression of the gut-homing chemokine receptor CCR9 on effector T cells in vitro. This suggests that CD103+ DCs might similarly induce CCR9 expression on T reg cells, thus endowing them with the ability to migrate to the gut—a possibility not yet tested in vivo.
But the effect of CD103 could also be indirect, suggests senior author Fiona Powrie. CD103 may help trap DCs in the gut by binding to its receptor (E-cadherin) on intestinal epithelial cells, consistent with the recent finding that CD103 is needed to retain pathogenic CD8+ T cells in the gut during graft versus host disease. Although this mechanism remains speculative, retention of DCs in the gut might be a prerequisite for endowing T reg cells with the ability to suppress.