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Langerhans Cell Homeostasis and Turnover After Nonmyeloablative and Myeloablative Allogeneic Hematopoietic Cell Transplantation

Lookup NU author(s): Professor Matthew CollinORCiD


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Background Langerhans cells (LCs) are self-renewing epidermal myeloid cells that can migrate and mature into dendritic cells. Recipient LCs that survive cytotoxic therapy given in preparation for allogeneic hematopoietic cell transplantation may prime donor T cells to mediate cutaneous graft-versus-host disease (GVHD). This possible association, however, has not been investigated in the setting of nonmyeloablative allografting.Methods We prospectively studied the kinetics of LC-chimerism after sex-mismatched allogeneic hematopoietic cell transplantation with nonmyeloablative (n=23) or myeloablative (n=25) conditioning. Combined XY-FISH and Langerin-staining was used to assess donor LC-chimerism in skin biopsies obtained on days 28, 56, and 84 after transplant. The degree of donor LC-chimerism was correlated with the development of skin GVHD.Results We observed significantly delayed donor LC-engraftment after nonmyeloablative transplantation compared with other hematopoietic compartments and compared with LC-engraftment after myeloablative conditioning. In most recipients of nonmyeloablative transplants, recipient LCs proliferated in situ, recruitment of donor-LCs was delayed by two months, and full donor LC-chimerism was only reached by day 84 after transplant. Although persistence of host LCs on day-28 after transplant was not predictive for acute or chronic skin GVHD, the recruitment of donor-derived LCs was associated with nonspecific inflammatory infiltrates (P=0.009).Conclusions These results show that LCs can self-renew locally but are replaced by circulating precursors even after minimally toxic nonmyeloablative transplant conditioning. Cutaneous inflammation accompanies donor LC-engraftment, but differences in LC conversion-kinetics do not predict clinical or histopathological GVHD.

Publication metadata

Author(s): Mielcarek M, Kirkorian AY, Hackman RC, Price J, Storer BE, Wood BL, Leboeuf M, Bogunovic M, Storb R, Inamoto Y, Flowers ME, Martin PJ, Collin M, Merad M

Publication type: Article

Publication status: Published

Journal: Transplantation

Year: 2014

Volume: 98

Issue: 5

Pages: 563-568

Print publication date: 15/09/2014

Acceptance date: 28/01/2014

ISSN (print): 0041-1337

ISSN (electronic): 1534-6080

Publisher: Lippincott Williams & Wilkins


DOI: 10.1097/TP.0000000000000097


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Funder referenceFunder name
Dana Foundation, Human Immunology Grant Program
CA018029National Institutes of Health, Bethesda, MD
CA078902National Institutes of Health, Bethesda, MD
CA015704National Institutes of Health, Bethesda, MD
HL108307National Institutes of Health, Bethesda, MD