title: G-CSF-treated donor CD4+ T cells attenuate acute GVHD through a reduction in Th17 cell differentiation.
abstract: The immunoregulatory effects of granulocyte colony-stimulating factor (G-CSF) on allogeneic peripheral blood cell transplantation (PBCT) have been demonstrated to reduce acute graft-versus-host disease (GVHD). However, the underlying mechanism is still not clear. In this study, we focused on the direct effects of G-CSF on donor CD4(+) T cell responses after transplantation. We observed that lethally irradiated B6D2F1 recipient mice that are transplanted with CD4(+) T cells from G-CSF-treated B6 donors showed mild attenuations in severity and mortality compared with recipients transplanted with PBS-treated CD4(+) T cells. Notably, skin GVHD was significantly reduced, but no such reduction was observed in other organs. Although there was no difference with respect to alloreactive expansion or Foxp3(+) Treg induction, the use of G-CSF-treated CD4(+) T cells significantly reduced the numbers of IL-17-producing and RORγt-expressing cells in the secondary lymphoid organs of allogeneic recipients after transplantation compared with the use of the control cells. Finally, we found that the suppressor of cytokine signaling-3 (SOCS3) expression in G-CSF-treated donor CD4(+) T cells was much higher than that in control CD4(+) T cells. Our results demonstrate that the inhibition of Th17 cell differentiation by SOCS3 induction is associated with the immunoregulatory role of G-CSF in CD4(+) T cell-mediated acute GVHD.
authors: Department of Hemato-Oncology, Haeundae Paik Hospital, Inje University, Busan 612-030, Republic of Korea.
authors: Young-Don
authors: YD
authors: Joo
authors: Won-Sik
authors: WS
authors: Lee
authors: Hae-Jeong
authors: HJ
authors: Won
authors: Soung-Min
authors: SM
authors: Lee
authors: Hye Ran
authors: HR
authors: Kim
authors: Ji Kyoung
authors: JK
authors: Park
authors: Sae-Gwang
authors: SG
authors: Park
authors: Il-Whan
authors: IW
authors: Choi
authors: Inhak
authors: I
authors: Choi
authors: Su-Kil
authors: SK
authors: Seo
mesh_terms: D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation*; D002454:Cell Differentiation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006086:Graft vs Host Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism*; D014184:Transplantation, Homologous
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016179:Granulocyte Colony-Stimulating Factor