STAT3 Expression in Host Myeloid Cells Controls Graft-versus-Host Disease Severity

Evelyn C. Nieves, Tomomi Toubai, Daniel C. Peltier, Katherine Oravecz-Wilson, Chen Liu, Hiroya Tamaki, Yaping Sun, Pavan Reddy

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Professional antigen-presenting cells (APCs) are important modulators of acute graft-versus-host disease (GVHD). Although dendritic cells (DCs) are the most potent APC subset, other myeloid cells, especially macrophages (MFs) and neutrophils, recently have been shown to play a role in the severity of GVHD. The critical molecular mechanisms that determine the functions of myeloid cells in GVHD are unclear, however. Signal transducer and activator of transcription 3 (STAT3) is a master transcription factor that plays a crucial role in regulating immunity, but its role in MF biology and in acute GVHD remains unknown. To determine the impact of myeloid cell-specific expression of STAT3 on the severity of acute GVHD, we used myeloid cell-specific STAT3-deficient LysM-Cre/STAT3fl/− animals as recipients and donors in well-characterized experimental models of acute GVHD. We found that reduced expression of STAT3 in myeloid cells from the hosts, but not the donors, increased inflammation, increased donor T cell activation, and exacerbated GVHD. Our data demonstrate that STAT3 in host myeloid cells, such as MFs, dampens acute GVHD.

Original languageEnglish (US)
Pages (from-to)1622-1630
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume23
Issue number10
DOIs
StatePublished - Oct 2017

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Keywords

  • Bone marrow transplantation
  • Graft-versus-host disease
  • Myeloid cells
  • STAT-3

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    Nieves, E. C., Toubai, T., Peltier, D. C., Oravecz-Wilson, K., Liu, C., Tamaki, H., Sun, Y., & Reddy, P. (2017). STAT3 Expression in Host Myeloid Cells Controls Graft-versus-Host Disease Severity. Biology of Blood and Marrow Transplantation, 23(10), 1622-1630. https://doi.org/10.1016/j.bbmt.2017.06.018