Stem cell mobilization with G-CSF induces type 17 differentiation and promotes scleroderma

Hill, Geoffrey R., Olver, Stuart D., Kuns, Rachel D., Varelias, Antiopi, Raffelt, Neil C., Don, Alistair L., Markey, Kate A., Wilson, Yana A., Smyth, Mark J., Iwakura, Yoichiro, Tocker, Joel, Clouston, Andrew D. and MacDonald, Kelli P. A. (2010) Stem cell mobilization with G-CSF induces type 17 differentiation and promotes scleroderma. Blood, 116 5: 819-828. doi:10.1182/blood-2009-11-256495

Author Hill, Geoffrey R.
Olver, Stuart D.
Kuns, Rachel D.
Varelias, Antiopi
Raffelt, Neil C.
Don, Alistair L.
Markey, Kate A.
Wilson, Yana A.
Smyth, Mark J.
Iwakura, Yoichiro
Tocker, Joel
Clouston, Andrew D.
MacDonald, Kelli P. A.
Title Stem cell mobilization with G-CSF induces type 17 differentiation and promotes scleroderma
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 2010-08-05
Sub-type Article (original research)
DOI 10.1182/blood-2009-11-256495
Volume 116
Issue 5
Start page 819
End page 828
Total pages 10
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Language eng
Abstract The recent shift to the use of stem cells mobilized by granulocyte colony-stimulating factor (G-CSF) for hematopoietic transplantation has increased chronic graftversus-host disease (GVHD), although the mechanisms of this are unclear. We have found that G-CSF invokes potent type 17 rather than type 1 or type 2 differentiation. The amplification of interleukin-17 (IL-17) production by G-CSF occurs in both CD4 and CD8 conventional T cells and is dependent on, and downstream of, G-CSF–induced IL-21 signaling. Importantly, donor IL-17A controls the infiltration of macrophages into skin and cutaneous fibrosis, manifesting late after transplantation as scleroderma. Interestingly, donor CD8 T cells were the predominant source of IL-17A after transplantation and could mediate scleroderma independently of CD4 T cells. This study provides a logical explanation for the propensity of allogeneic stem cell transplantation to invoke sclerodermatous GVHD and suggests a therapeutic strategy for intervention.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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