Mast Cells Are Mediators of Fibrosis and Effector Cell Recruitment in Dermal Chronic Graft-vs.-Host Disease

Ethan Strattan, Senthilnathan Palaniyandi, Reena Kumari, Jing Du, Natalya Hakim, Timothy Huang, Melissa V. Kesler, C. Darrell Jennings, Jamie L. Sturgill, Gerhard C. Hildebrandt

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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-vs.-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.

Original languageEnglish
Article number2470
JournalFrontiers in Immunology
Volume10
DOIs
StatePublished - Oct 18 2019

Bibliographical note

Funding Information:
This research was supported by the following core labs: Flow Cytometry and Cell Sorting Shared Resource Facility, Biospecimen Procurement and Translational Pathology Shared Resource Facility, and the Oncogenomics Shared Resource Facility, all through the University of Kentucky Markey Cancer Center (P30CA177558). Research reported in this publication was also supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103527, and Aperio services were supported through the NIA/NIH ADC P30 AGO28383. Funding. This study was supported via Investigator Support Funds from the University of Kentucky/Markey Cancer Center awarded to GH.

Funding Information:
This study was supported via Investigator Support Funds from the University of Kentucky/Markey Cancer Center awarded to GH.

Funding Information:
This research was supported by the following core labs: Flow Cytometry and Cell Sorting Shared Resource Facility, Biospecimen Procurement and Translational Pathology Shared Resource Facility, and the Oncogenomics Shared Resource Facility, all through the University of Kentucky Markey Cancer Center (P30CA177558). Research reported in this publication was also supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103527, and Aperio services were supported through the NIA/NIH ADC P30 AGO28383.

Publisher Copyright:
© Copyright © 2019 Strattan, Palaniyandi, Kumari, Du, Hakim, Huang, Kesler, Jennings, Sturgill and Hildebrandt.

Keywords

  • GVHD
  • fibrosis
  • immunity
  • mast cells
  • skin
  • transplant

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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