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


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.

SUBMITTER: Laurence A 

PROVIDER: S-EPMC3441059 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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

Laurence Arian A   Amarnath Shoba S   Mariotti Jacopo J   Kim Yong Chan YC   Foley Jason J   Eckhaus Michael M   O'Shea John J JJ   Fowler Daniel H DH  

Immunity 20120801 2


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  ...[more]

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