PMID- 25079358
OWN - NLM
STAT- MEDLINE
DCOM- 20150930
LR  - 20211021
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 124
IP  - 12
DP  - 2014 Sep 18
TI  - Absence of STAT1 in donor-derived plasmacytoid dendritic cells results in 
      increased STAT3 and attenuates murine GVHD.
PG  - 1976-86
LID - 10.1182/blood-2013-05-500876 [doi]
AB  - Selective targeting of non-T cells, including antigen-presenting cells (APCs), is 
      a potential strategy to prevent graft-versus-host-disease (GVHD) but to maintain 
      graft-versus-tumor (GVT) effects. Because type I and II interferons signal 
      through signal transducer and activator of transcription-1 (STAT1), and 
      contribute to activation of APCs after allogeneic bone marrow transplant 
      (alloBMT), we examined whether the absence of STAT1 in donor APCs could prevent 
      GVHD while preserving immune competence. Transplantation of STAT1(-/-) bone 
      marrow (BM) prevented GVHD induced by STAT1(+/+) T cells, leading to expansion of 
      B220(+) cells and regulatory T cells. STAT1(-/-) BM also preserved GVT activity 
      and enhanced overall survival of tumor-challenged mice in the setting of GVHD. 
      Furthermore, recipients of allogeneic STAT1(-/-) BM demonstrated increased 
      CD9(-)Siglec H(hi) plasmacytoid dendritic cells (pDCs), and depletion of pDCs 
      after STAT1(-/-) BM transplantation prevented GVHD resistance. STAT1(-/-) pDCs 
      were found to produce decreased free radicals, IFNalpha, and interleukin (IL)-12, and 
      increased IL-10. Additionally, STAT1(-/-) pDCs that were isolated after alloBMT 
      showed increased gene expression of S100A8 and S100A9, and transplantation of 
      S100A9(-/-) BM reduced GVHD-free survival. Finally, elevated STAT3 was found in 
      STAT1(-/-) pDCs isolated after alloBMT. We conclude that interfering with 
      interferon signaling in APCs such as pDCs provides a novel approach to regulate 
      the GVHD/GVT axis.
FAU - Capitini, Christian M
AU  - Capitini CM
AUID- ORCID: 0000-0002-2276-6731
AD  - Department of Pediatrics and Carbone Cancer Center, University of Wisconsin 
      School of Medicine and Public Health, Madison, WI;
FAU - Nasholm, Nicole M
AU  - Nasholm NM
AD  - Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      and.
FAU - Chien, Christopher D
AU  - Chien CD
AD  - Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      and.
FAU - Larabee, Shannon M
AU  - Larabee SM
AD  - Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      and.
FAU - Qin, Haiying
AU  - Qin H
AD  - Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      and.
FAU - Song, Young K
AU  - Song YK
AD  - Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      and.
FAU - Klover, Peter J
AU  - Klover PJ
AD  - Laboratory of Genetics and Physiology, National Institute of Diabetes and 
      Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
FAU - Hennighausen, Lothar
AU  - Hennighausen L
AD  - Laboratory of Genetics and Physiology, National Institute of Diabetes and 
      Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
FAU - Khan, Javed
AU  - Khan J
AD  - Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      and.
FAU - Fry, Terry J
AU  - Fry TJ
AD  - Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      and.
LA  - eng
GR  - K08 CA174750/CA/NCI NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140725
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Calgranulin A)
RN  - 0 (Calgranulin B)
RN  - 0 (S100A9 protein, mouse)
RN  - 0 (S100a8 protein, mouse)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat1 protein, mouse)
RN  - 0 (Stat3 protein, mouse)
SB  - IM
CIN - Blood. 2014 Sep 18;124(12):1852-3. PMID: 25606629
MH  - Allografts
MH  - Animals
MH  - Bone Marrow Transplantation/adverse effects
MH  - Calgranulin A/genetics
MH  - Calgranulin B/genetics/metabolism
MH  - Dendritic Cells/immunology/*metabolism/*transplantation
MH  - Female
MH  - Gene Expression
MH  - Graft vs Host Disease/etiology/metabolism/*prevention & control
MH  - Male
MH  - Mice
MH  - Mice, 129 Strain
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - STAT1 Transcription Factor/*deficiency/genetics
MH  - STAT3 Transcription Factor/*metabolism
MH  - T-Lymphocytes/immunology/metabolism
MH  - Tissue Donors
PMC - PMC4168352
EDAT- 2014/08/01 06:00
MHDA- 2015/10/01 06:00
PMCR- 2015/09/18
CRDT- 2014/08/01 06:00
PHST- 2014/08/01 06:00 [entrez]
PHST- 2014/08/01 06:00 [pubmed]
PHST- 2015/10/01 06:00 [medline]
PHST- 2015/09/18 00:00 [pmc-release]
AID - S0006-4971(20)39747-0 [pii]
AID - 2013/500876 [pii]
AID - 10.1182/blood-2013-05-500876 [doi]
PST - ppublish
SO  - Blood. 2014 Sep 18;124(12):1976-86. doi: 10.1182/blood-2013-05-500876. Epub 2014 
      Jul 25.