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Cited by 201T-cell and B-cell ImmunologyHematopoietic Stem Cell TransplantationRenal Transplantation Outcomes and Treatments

STAT3 transcription factor promotes instability of nTreg cells and limits generation of iTreg cells during acute murine graft-versus-host disease

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Laurence, Arian, Amarnath, Shoba, Mariotti, Jacopo, Kim, Yong Chan, Foley, Jason, Eckhaus, Michael, O'Shea, John J., Fowler, Daniel H.·2012·Immunity
DOI 10.1016/j.immuni.2012.05.027PMC PMC3441059
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Abstract

Acute graft-versus-host disease (GvHD) is a major cause of mortality in allogeneic bone marrow transplantation (BMT), for which administration of FoxP3(+) regulatory T (Treg) cells has been proposed as a therapy. However, the phenotypic stability of Treg cells is controversial, and STAT3-dependent cytokines can inhibit FoxP3 expression. We assessed whether the elimination of STAT3 in T cells could limit the severity of GvHD. We found STAT3 limited FoxP3(+) Treg cell numbers following allogeneic BMT by two pathways: instability of natural Treg (nTreg) cells and inhibition of induced Treg (iTreg) cell polarization from naive CD4(+) T cells. Deletion of STAT3 within only the nTreg cell population was not sufficient to protect against lethal GvHD. In contrast, transfer of STAT3-deficient naive CD4(+) T cells increased FoxP3(+) Treg cells post-BMT and prevented lethality, suggesting that the consequence of STAT3 signaling may be greater for iTreg rather than nTreg cells during GvHD.

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Authors
Laurence, A., Amarnath, S., Mariotti, J., Kim, Y. C., Foley, J., Eckhaus, M., O'Shea, J. J., & Fowler, D. H.
Affiliations
National Institutes of Health (US)
Corresponding author
Laurence, Arian
ORCID
Venue
Immunity
Publisher
Elsevier BV
Published
2012-08
Volume
37
Issue
2
Pages
209-222
ISSN
1074-7613 (ISSN-L)
DOI
10.1016/j.immuni.2012.05.027
PMC
PMC3441059
OpenAlex
W2084117111
Cited by
201
References
49
Citations by year
2026: 10 · 2025: 10 · 2024: 14 · 2023: 13 · 2022: 6 · 2021: 16 · 2020: 7 · 2019: 10 · 2018: 13 · 2017: 15 · 2016: 23 · 2015: 21 · 2014: 21 · 2013: 21
FWCI
8.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
National Institutes of Health (Z99‐AA999999, Z99 AR999999, Z99 DA999999)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
Keywords
STAT3, graft-versus-host disease, regulatory T cells, induced Treg cells, Foxp3, allogeneic bone marrow transplantation, CD4+ T cell differentiation, Treg therapy
MeSH terms
Animals, Disease Models, Animal, Flow Cytometry, Graft vs Host Disease, T-Lymphocytes, Helper-Inducer, Humans, Mice, Inbred BALB C, Mice, Inbred C57BL, Signal Transduction, Bone Marrow Transplantation, Cytokines, Mice, Knockout, Chromatin Immunoprecipitation, T-Lymphocytes, Regulatory, STAT3 Transcription Factor, Mice, Forkhead Transcription Factors

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