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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02470

Mast cells are mediators of fibrosis and effector cell recruitment in dermal chronic graft-versus-host disease

 Ethan Strattan1, 2, Senthilnathan Palaniyandi3, Reena Kumari3, Jing Du4, Natalya Hakim4,  Timothy Huang3, Melissa V. Kesler4, C. D. Jennings4, Jamie L. Sturgill2 and Gerhard C. Hildebrandt3*
  • 1Division of Hematology and Blood and Marrow Transplantation, University of Kentucky, United States
  • 2Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, United States
  • 3Division of Hematology and Blood & Marrow Transplant, University of Kentucky, United States
  • 4Department of Pathology, University of Kentucky, United States

Allogeneic hematopoietic stem cell transplant (allo-HSCT) is often used to treat acute leukemia or defects of hematopoiesis. Its widespread use is hampered by graft-versus-host disease (GVHD), which has high morbidity and mortality in both acute and chronic subtypes. Chronic GVHD (cGVHD) occurs most frequently in skin and often is characterized by pathogenic fibrosis. Mast cells (MCs) are known to be involved in the pathogenesis of other fibrotic diseases. In a murine model of cGVHD after allo-HSCT, C57BL/6J recipients of allogeneic LP/J donor cells develop sclerodermatous dermal cGVHD which is significantly decreased in mast cell-deficient B6.Cg-KitW-sh/HNihrJaeBsmGlliJ recipients. The presence of MCs is associated with fibrosis, chemokine production, and recruitment of GVHD effector cells to the skin. Chemokine production by MCs is blocked by drugs used to treat cGVHD. The importance of MCs in skin cGVHD is mirrored by increased MCs in the skin of patients with dermal cGVHD. We show for the first time a role for MCs in skin cGVHD that may be targetable for preventive and therapeutic intervention in this disease.

Keywords: GvHD, Fibrosis, Mast Cells, Skin, transplant, Immunity

Received: 02 Jul 2019; Accepted: 03 Oct 2019.

Copyright: © 2019 Strattan, Palaniyandi, Kumari, Du, Hakim, Huang, Kesler, Jennings, Sturgill and Hildebrandt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Gerhard C. Hildebrandt, University of Kentucky, Division of Hematology and Blood & Marrow Transplant, Lexington, 40506, Kentucky, United States, gerhard.hildebrandt@uky.edu