Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men

Abstract

In this study, we explored dermal dendritic cell (DC) homeostasis in mice and humans both in the steady state and after hematopoietic cell transplantation. We 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 >6 mo. In lethally irradiated mice injected with donor congenic bone marrow (BM) 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, our results oppose the traditional view that DCs are nondividing 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.

Characteristics and functions of murine cutaneous dendritic cells: a synopsis of recent developments

“…Under steady-state conditions, LCs appear to derive from radioresistant cells that slowly proliferate within the skin. 22 The precise nature of these precursors has yet to be defined, but the observation that M-CSFR-deficient mice are also LC deficient is consistent with the hypothesis that steady-state LC could be derived from monocytes. 23 The characteristics of LC precursors in the setting of GvHD and / or ultraviolet-induced LC depletion and inflammation are better defined.…”

Dendritic cells in the thymus contribute to T-regulatory cell induction

“…Because some DCs are radioresistant, it was important to establish whether TDCs in the chimeras were all of donor origin (27,28). Staining the TDC-enriched light density cell fraction for donorderived DCs 6 weeks after BM reconstitution demonstrated that Ͼ98% of DCs were of donor origin (MHCII Ϫ ), indicating effective elimination of host DCs (Fig.…”

Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress

“…Generation of BM chimeras was performed as previously described (46). Animals were given an injection of ketamine (100 mg/kg) and xylazine (10 mg/kg), and their heads were placed in lead shields (Nuclead) to protect the brain.…”