A possible role for CCL27/CTACK-CCR10 interaction in recruiting CD4+ T cells to skin in human graft-versus-host disease
Claudia M. J. M. Faaij
Department of Paediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Centre (LUMC)
Search for more papers by this authorArjan C. Lankester
Department of Paediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Centre (LUMC)
Search for more papers by this authorEric Spierings
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre (LUMC), Leiden, the Netherlands
Search for more papers by this authorManja Hoogeboom
Department of Paediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Centre (LUMC)
Search for more papers by this authorMarc Bierings
Department of Paediatric Haematology and Stem Cell Transplantation, University Medical Centre, Utrecht, the Netherlands
Search for more papers by this authorTom Révész
Department of Paediatric Haematology and Stem Cell Transplantation, University Medical Centre, Utrecht, the Netherlands
Search for more papers by this authorR. Maarten Egeler
Department of Paediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Centre (LUMC)
Search for more papers by this authorMaarten J. D. Van Tol
Department of Paediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Centre (LUMC)
Search for more papers by this authorNicola E. Annels
Department of Paediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Centre (LUMC)
Search for more papers by this authorClaudia M. J. M. Faaij
Department of Paediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Centre (LUMC)
Search for more papers by this authorArjan C. Lankester
Department of Paediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Centre (LUMC)
Search for more papers by this authorEric Spierings
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre (LUMC), Leiden, the Netherlands
Search for more papers by this authorManja Hoogeboom
Department of Paediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Centre (LUMC)
Search for more papers by this authorMarc Bierings
Department of Paediatric Haematology and Stem Cell Transplantation, University Medical Centre, Utrecht, the Netherlands
Search for more papers by this authorTom Révész
Department of Paediatric Haematology and Stem Cell Transplantation, University Medical Centre, Utrecht, the Netherlands
Search for more papers by this authorR. Maarten Egeler
Department of Paediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Centre (LUMC)
Search for more papers by this authorMaarten J. D. Van Tol
Department of Paediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Centre (LUMC)
Search for more papers by this authorNicola E. Annels
Department of Paediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Centre (LUMC)
Search for more papers by this authorSummary
Graft-versus-host disease (GvHD) is a serious complication of allogeneic stem cell transplantation (SCT) affecting the skin, gut and liver. The involvement of distinct organs suggests a role for tissue-specific chemokines and their receptors in directing activated donor T cells to these sites. In this study the potential involvement of the skin-specific CCL27/CTACK-CCR10 interaction was investigated in 15 paediatric SCT patients with skin GvHD. During the course of skin GvHD, peripheral blood T cells from these patients contained a high proportion of CD4+ CCR10+ T cells that disappeared after the GvHD was resolved. These cells were CD45RO+, expressed additional skin homing markers (cutaneous lymphocyte-associated antigen and CCR4), and produced the T-cell helper type 1-cytokines tumour necrosis factor-alpha and interleukin-2. The increase in CD4+ CCR10+ T cells was absent in SCT patients without GvHD. Immunohistochemical investigations showed CD4+ CCR10+ T cells in the GvHD skin biopsies of the same patients, but not in the gut biopsies of patients also suffering from gut GvHD. The infiltration of CD4+ CCR10+ T cells in the GvHD-affected skin correlated with an enhanced epidermal expression of CCL27/CTACK, the ligand for CCR10. These findings support the involvement of CCL27/CTACK-CCR10 interaction in recruiting CD4+ T cells to the skin, thus contributing to the pathogenesis of acute GvHD.
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