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 Citations (Scopus)

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/STAT3 fl/− 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 1 2017

Fingerprint

STAT3 Transcription Factor
Graft vs Host Disease
Myeloid Cells
Antigen-Presenting Cells
Dendritic Cells
Immunity
Neutrophils
Transcription Factors
Theoretical Models
Macrophages
Inflammation
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Hematology
  • Transplantation

Keywords

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

Cite this

Nieves, E. C., Toubai, T., Peltier, D. C., Oravecz-Wilson, K., Liu, C., Tamaki, H., ... 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
Nieves, Evelyn C. ; Toubai, Tomomi ; Peltier, Daniel C. ; Oravecz-Wilson, Katherine ; Liu, Chen ; Tamaki, Hiroya ; Sun, Yaping ; Reddy, Pavan. / STAT3 Expression in Host Myeloid Cells Controls Graft-versus-Host Disease Severity. In: Biology of Blood and Marrow Transplantation. 2017 ; Vol. 23, No. 10. pp. 1622-1630.
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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/STAT3 fl/− 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.",
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Nieves, EC, Toubai, T, Peltier, DC, 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, vol. 23, no. 10, pp. 1622-1630. https://doi.org/10.1016/j.bbmt.2017.06.018

STAT3 Expression in Host Myeloid Cells Controls Graft-versus-Host Disease Severity. / Nieves, Evelyn C.; Toubai, Tomomi; Peltier, Daniel C.; Oravecz-Wilson, Katherine; Liu, Chen; Tamaki, Hiroya; Sun, Yaping; Reddy, Pavan.

In: Biology of Blood and Marrow Transplantation, Vol. 23, No. 10, 01.10.2017, p. 1622-1630.

Research output: Contribution to journalArticle

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AU - Toubai, Tomomi

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AU - Liu, Chen

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AU - Reddy, Pavan

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