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

doi:10.3389/fimmu.2019.02470

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 journal › Article › peer-review

15 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-Kit^W−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 language	English
Article number	2470
Journal	Frontiers in Immunology
Volume	10
DOIs	https://doi.org/10.3389/fimmu.2019.02470
State	Published - Oct 18 2019

Bibliographical note

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

Funding

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

Funders	Funder number
PPD Investigator Services LLC
NIA/NIH	ADC P30 AGO28383
University of Kentucky Markey Cancer Center
National Institutes of Health (NIH)
National Institute of General Medical Sciences	P20GM103527
Center for Outcomes Research and Evaluation, Yale School of Medicine
University of Kentucky Markey Cancer Center	P30CA177558

Keywords

GVHD
fibrosis
immunity
mast cells
skin
transplant

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.3389/fimmu.2019.02470

Cite this

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

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.",

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

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doi = "10.3389/fimmu.2019.02470",

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AU - Kumari, Reena

AU - Du, Jing

AU - Hakim, Natalya

AU - Huang, Timothy

AU - Kesler, Melissa V.

AU - Jennings, C. Darrell

AU - Sturgill, Jamie L.

AU - Hildebrandt, Gerhard C.

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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