STAT3 Transcription Factor Promotes Instability of NTreg Cells and Limits Generation of ITreg Cells During Acute Murine Graft-versus-host Disease

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2012 Aug 28

PMID 22921119

Citations 116

Authors

Arian Laurence

Shoba Amarnath

Jacopo Mariotti

Yong Chan Kim

Jason Foley

Michael Eckhaus

John J OShea

Daniel H Fowler

Affiliations

Soon will be listed here.

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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