As the only dendritic cells resident in the epidermis, Langerhans cells (LCs) play a critical role in skin immunity. Through their stimulation of donor T cells, LCs likely play a key role in skin graft-versus-host-disease (GVHD), a serious complication that limits the use of allogeneic bone marrow (BM) transplantation. Despite their importance, little is known about the life cycle of LCs, their precursor cells in the blood and their homeostasis after allogeneic BM transplantation. Furthermore, the mechanisms by which LCs influence GVHD have not been elucidated. We have recently established that LCs are maintained by a radio-resistant precursor that self-renew in quiescent skin throughout life. In contrast, LCs are replaced by circulating precursors after major skin injury such as exposure to UV light or donor allo-reactive T cells infiltration. In addition we have recently characterized the circulating LC precursor that repopulate LCs in UV injured skin. We hypothesize that this unique cycle of LC homeostasis; controls skin allogeneic immune responses after transplantation. To address our hypothesis, we will employ complementary approaches using adoptive transfer of hematopoietic precursors in mice and a clinically relevant model for allogeneic hematopoietic stem cell transplantation.
Aim 1, will characterize the direct circulating precursor that repopulate skin resident LCs after allo-BMT.
Aim 2, will characterize the mechanisms leading to the replacement of host LCs by donor LCs after allog-BMT.
Aim 3 Will explore the immunological mechanisms that lead to the protective effect of LC chimerism on skin GVHD. These studies should provide valuable insights into LC regulation of skin immune responses and may lead to improved prevention or treatment of skin GVHD, a major medical problem in transplantation therapy of patients with malignancies. ? ? ?

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Cancer Immunopathology and Immunotherapy Study Section (CII)
Program Officer
Mccarthy, Susan A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mount Sinai School of Medicine
Internal Medicine/Medicine
Schools of Medicine
New York
United States
Zip Code
Jiao, Jingjing; Ooka, Kohtaro; Fey, Holger et al. (2016) Interleukin-15 receptor ? on hepatic stellate cells regulates hepatic fibrogenesis in mice. J Hepatol 65:344-353
Hoeffel, Guillaume; Chen, Jinmiao; Lavin, Yonit et al. (2015) C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity 42:665-78
Chow, Andrew; Huggins, Matthew; Ahmed, Jalal et al. (2013) CD169? macrophages provide a niche promoting erythropoiesis under homeostasis and stress. Nat Med 19:429-36
Hoeffel, Guillaume; Wang, Yilin; Greter, Melanie et al. (2012) Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J Exp Med 209:1167-81
Jiao, Jingjing; Sastre, David; Fiel, Maria Isabel et al. (2012) Dendritic cell regulation of carbon tetrachloride-induced murine liver fibrosis regression. Hepatology 55:244-55
Greter, Melanie; Lelios, Iva; Pelczar, Pawel et al. (2012) Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia. Immunity 37:1050-1060
Kwan, Wing-Hong; Hashimoto, Daigo; Paz-Artal, Estela et al. (2012) Antigen-presenting cell-derived complement modulates graft-versus-host disease. J Clin Invest 122:2234-8
Hashimoto, Daigo; Chow, Andrew; Greter, Melanie et al. (2011) Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation. J Exp Med 208:1069-82
Chow, Andrew; Brown, Brian D; Merad, Miriam (2011) Studying the mononuclear phagocyte system in the molecular age. Nat Rev Immunol 11:788-98
Chow, Andrew; Lucas, Daniel; Hidalgo, Andrés et al. (2011) Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J Exp Med 208:261-71

Showing the most recent 10 out of 20 publications