TY - JOUR
T1 - Mast Cells Are Mediators of Fibrosis and Effector Cell Recruitment in Dermal Chronic Graft-vs.-Host Disease
AU - Strattan, Ethan
AU - Palaniyandi, Senthilnathan
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.
N1 - Publisher Copyright:
© Copyright © 2019 Strattan, Palaniyandi, Kumari, Du, Hakim, Huang, Kesler, Jennings, Sturgill and Hildebrandt.
PY - 2019/10/18
Y1 - 2019/10/18
N2 - 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.
AB - 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.
KW - GVHD
KW - fibrosis
KW - immunity
KW - mast cells
KW - skin
KW - transplant
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U2 - 10.3389/fimmu.2019.02470
DO - 10.3389/fimmu.2019.02470
M3 - Article
C2 - 31681336
AN - SCOPUS:85074433096
VL - 10
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 2470
ER -