In this paper, Bogunovic and colleagues explored dermal DC homeostasis in mice and humans both in the steady state and after hematopoietic cell transplantation. They discovered that dermal DCs proliferate in situ in mice and human quiescent dermis. In parabiotic mice with separate organs but shared blood circulation, the majority of dermal DCs failed to be replaced by circulating precursors for more than six months. In lethally irradiated mice injected with donor congenic bone marrow cells, a subset of recipient DCs remained in the dermis and proliferated locally throughout life. Consistent with these findings, a large proportion of recipient dermal DCs remained in patients’ skin after allogeneic hematopoietic cell transplantation, despite complete donor BM chimerism. Collectively, these results oppose the traditional view that DCs are non-dividing terminally differentiated cells maintained by circulating precursors and support the new paradigm that tissue DCs have local proliferative properties that control their homeostasis in the steady state. Given the role of residual host tissue DCs in transplant immune reactions, these results suggest that dermal DC homeostasis may contribute to the development of cutaneous graft-versus-host disease in clinical transplantation.
This has to be paralleled to a study published by Collin et al. in which the investigators followed the fate of human LC with the aim to define the effect of conditioning regimes and GVHD in the survival of recipient LC and reconstitution of donor cells after transplant. Confocal microscopy of epidermal sheets shows that full intensity transplant depletes LC more rapidly than reduced intensity transplant. Recovery occurs rapidly within 40 days in the absence of acute GVHD, but was delayed beyond 100 days when GVHD is active. At 100 days, all transplants achieve at least 90 percent LC donor chimerism and over half achieve 100 percent. Complete donor chimerism was associated with prior acute cutaneous GVHD, suggesting a role for allogeneic T cells in promoting LC engraftment.
In Brief
Whether recipient DCs play a role in the initiation or as target of a GVHD reaction remains to be determined. These studies are critically needed as they should help to determine the need for novel conditioning therapies aimed at reducing the pool of residual recipient DCs as a means of improving GVHD outcome in clinical transplantation. However, when considering the negative impact of residual recipient DCs in GVHD, it is critical to keep in mind that these cells are likely to participate in the generation of potent anti-tumor immune responses and that their elimination may also reduce the graft-versus-tumor effect. Thus, it is conceivable that therapies targeted to tissues that are most affected by GVHD and, where persistence of a large pool of residual recipient DCs has been demonstrated (i.e., the skin), may help improve local tissue damage caused by GVHD without hampering a systemic graft-versus-tumor effect. Targeted cutaneous therapies could include the use of UV light, antibodies to cutaneous DCs, or electron beam therapy.
Competing Interests
Dr. Socié indicated no relevant conflicts of interest.
