Langerhans cell homeostasis and turnover after nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation

Marco Mielcarek, Anna Yasmine Kirkorian, Robert C. Hackman, Jeremy Price, Barry E. Storer, Brent L. Wood, Marylene Leboeuf, Milena Bogunovic, Rainer Storb, Yoshihiro Inamoto, Mary E. Flowers, Paul J. Martin, Matthew Collin, Miriam Merad

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)563-568
Number of pages6
JournalTransplantation
Volume98
Issue number5
DOIs
StatePublished - Jan 1 2014

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Langerhans Cells
Cell Transplantation
Homeostasis
Tissue Donors
Chimerism
Graft vs Host Disease
Skin
Transplants
Poisons
Homologous Transplantation
Myeloid Cells
Dendritic Cells

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Mielcarek, M., Kirkorian, A. Y., Hackman, R. C., Price, J., Storer, B. E., Wood, B. L., ... Merad, M. (2014). Langerhans cell homeostasis and turnover after nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation. Transplantation, 98(5), 563-568. https://doi.org/10.1097/TP.0000000000000097
Mielcarek, Marco ; Kirkorian, Anna Yasmine ; Hackman, Robert C. ; Price, Jeremy ; Storer, Barry E. ; Wood, Brent L. ; Leboeuf, Marylene ; Bogunovic, Milena ; Storb, Rainer ; Inamoto, Yoshihiro ; Flowers, Mary E. ; Martin, Paul J. ; Collin, Matthew ; Merad, Miriam. / Langerhans cell homeostasis and turnover after nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation. In: Transplantation. 2014 ; Vol. 98, No. 5. pp. 563-568.
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title = "Langerhans cell homeostasis and turnover after nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation",
abstract = "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.",
author = "Marco Mielcarek and Kirkorian, {Anna Yasmine} and Hackman, {Robert C.} and Jeremy Price and Storer, {Barry E.} and Wood, {Brent L.} and Marylene Leboeuf and Milena Bogunovic and Rainer Storb and Yoshihiro Inamoto and Flowers, {Mary E.} and Martin, {Paul J.} and Matthew Collin and Miriam Merad",
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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 2014, 'Langerhans cell homeostasis and turnover after nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation', Transplantation, vol. 98, no. 5, pp. 563-568. https://doi.org/10.1097/TP.0000000000000097

Langerhans cell homeostasis and turnover after nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation. / Mielcarek, Marco; Kirkorian, Anna Yasmine; Hackman, Robert C.; Price, Jeremy; Storer, Barry E.; Wood, Brent L.; Leboeuf, Marylene; Bogunovic, Milena; Storb, Rainer; Inamoto, Yoshihiro; Flowers, Mary E.; Martin, Paul J.; Collin, Matthew; Merad, Miriam.

In: Transplantation, Vol. 98, No. 5, 01.01.2014, p. 563-568.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Langerhans cell homeostasis and turnover after nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation

AU - Mielcarek, Marco

AU - Kirkorian, Anna Yasmine

AU - Hackman, Robert C.

AU - Price, Jeremy

AU - Storer, Barry E.

AU - Wood, Brent L.

AU - Leboeuf, Marylene

AU - Bogunovic, Milena

AU - Storb, Rainer

AU - Inamoto, Yoshihiro

AU - Flowers, Mary E.

AU - Martin, Paul J.

AU - Collin, Matthew

AU - Merad, Miriam

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

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