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

作者：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^*

来源：Blood, 2010, 116(5): 819-828.

DOI：10.1182/blood-2009-11-256495

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. (Blood. 2010;116(5):819-828)

• 出版日期2010-8-5
• 单位河北医科大学