Article abstract

Nature Immunology 9, 1347 - 1355 (2008)
Published online: 9 November 2008 | Corrected online: 9 April 2009 | doi:10.1038/ni.1677



There is an Erratum (May 2009) associated with this Article.

IL-4 inhibits TGF-bold beta-induced Foxp3+ T cells and, together with TGF-bold beta, generates IL-9+ IL-10+ Foxp3- effector T cells

Valérie Dardalhon1,2,6, Amit Awasthi1,2,6, Hyoung Kwon1, George Galileos1, Wenda Gao3, Raymond A Sobel4, Meike Mitsdoerffer2, Terry B Strom3, Wassim Elyaman2, I-Cheng Ho5, Samia Khoury2, Mohamed Oukka1 & Vijay K Kuchroo2

Transcription factor Foxp3 is critical for generating regulatory T cells (Treg cells). Transforming growth factor-beta (TGF-beta) induces Foxp3 and suppressive Treg cells from naive T cells, whereas interleukin 6 (IL-6) inhibits the generation of inducible Treg cells. Here we show that IL-4 blocked the generation of TGF-beta-induced Foxp3+ Treg cells and instead induced a population of T helper cells that produced IL-9 and IL-10. The IL-9+IL-10+ T cells demonstrated no regulatory properties despite producing abundant IL-10. Adoptive transfer of IL-9+IL-10+ T cells into recombination-activating gene 1–deficient mice induced colitis and peripheral neuritis, the severity of which was aggravated if the IL-9+IL-10+ T cells were transferred with CD45RBhi CD4+ effector T cells. Thus IL-9+IL-10+ T cells lack suppressive function and constitute a distinct population of helper-effector T cells that promote tissue inflammation.

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  1. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA.
  2. Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
  3. Transplant Research Center, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
  4. Palo Alto Veteran's Administration Health Care System and Department of Pathology, Stanford University School of Medicine, Palo Alto, California 94304, USA.
  5. Division of Pediatric Hematology-Oncology, Children's Hospital, Department of Pediatric Oncology, Harvard Medical School, Boston, Massachusetts 02115, USA.
  6. These authors contributed equally to this work.

Correspondence to: Mohamed Oukka1 e-mail: moukka@rics.bwh.harvard.edu

Correspondence to: Vijay K Kuchroo2 e-mail: vkuchroo@rics.bwh.harvard.edu

* In the version of this article initially published, graph axes are mislabeled in Figures 1e, 2d and 2e, and a gene symbol is misidentified in the legend to Figure 2. The correct axis labels should be as follows: Figure 1e, middle right and far right vertical axes should end "(relative x 103)"; Figure 2d,e, left vertical axes should read "Il9 mRNA (relative x 102)"; Figure 2e, right vertical axis should read "Il10 mRNA (relative)"; and Figure 2e, horizontal axes should read "WT" (in place of "Foxp3-GFP") and "GATA3-KO" (in place of "STAT6-KO.Fox3-GFP"). The legend for Figure 2d should state "relative to Hprt1 mRNA" and the legend to Figure 2e should have that phrase removed. The errors have been corrected in the HTML and PDF versions of the article.

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