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De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells

An Erratum to this article was published on 07 April 2015

This article has been updated


Interleukin-17 (IL-17)-secreting T cells of the T helper 17 (TH17) lineage play a pathogenic role in multiple inflammatory and autoimmune conditions and thus represent a highly attractive target for therapeutic intervention. We report that inhibition of acetyl-CoA carboxylase 1 (ACC1) restrains the formation of human and mouse TH17 cells and promotes the development of anti-inflammatory Foxp3+ regulatory T (Treg) cells. We show that TH17 cells, but not Treg cells, depend on ACC1-mediated de novo fatty acid synthesis and the underlying glycolytic-lipogenic metabolic pathway for their development. Although TH17 cells use this pathway to produce phospholipids for cellular membranes, Treg cells readily take up exogenous fatty acids for this purpose. Notably, pharmacologic inhibition or T cell–specific deletion of ACC1 not only blocks de novo fatty acid synthesis but also interferes with the metabolic flux of glucose-derived carbon via glycolysis and the tricarboxylic acid cycle. In vivo, treatment with the ACC-specific inhibitor soraphen A or T cell–specific deletion of ACC1 in mice attenuates TH17 cell–mediated autoimmune disease. Our results indicate fundamental differences between TH17 cells and Treg cells regarding their dependency on ACC1-mediated de novo fatty acid synthesis, which might be exploited as a new strategy for metabolic immune modulation of TH17 cell–mediated inflammatory diseases.

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Figure 1: SorA restrains TH17 cell differentiation and promotes Treg cell development.
Figure 2: ACC1 inhibition alters the transcriptional and metabolic signature of TH17 cells and reduces their proliferative capacity.
Figure 3: ACC1 inhibition blocks the glycolytic-lipogenic pathway.
Figure 4: Inhibition of ACC1 attenuates mouse TH17 cell–mediated autoimmune disease and regulates human TH17 and Treg cell fate.

Change history

  • 31 October 2014

     In the version of this article initially published online, the number 21.45, corresponding to the percentage of cells, was missing from the bottom right quadrant of the flow cytometry plot (SorA, WT) in Figure 2a. The error has been corrected for the print, PDF and HTML versions of this article.


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We thank S.J. Wakil (Baylor College of Medicine) for providing ACC1lox and ACC2-knockout mice, M. Swallow for critical reading of the manuscript and all members of the Institute of Infection Immunology at TWINCORE for discussion and support. We would like to acknowledge the assistance of the Cell Sorting Core Facility of the Hannover Medical School supported in part by the Braukmann-Wittenberg-Herz-Stiftung and the Deutsche Forschungsgemeinschaft. We thank E. Surges for excellent technical help, B. Beckmann for support using the Seahorse XF Analyzer, F. Sasse (Helmholtz Centre for Infection Research) for providing SorA and M. Haidukiewicz (Hannover Medical School) for providing human cord blood. This work was supported by grants from the Deutsche Forschungsgemeinschaft (LO1415/2-1, KFO250 and SFB900 to T.S. and M.L. and PO732 to E.P.) and the Novartis Research Foundation to M.L.; A.N. was supported by the German academic exchange service and C.T.M. by the German National Academic Foundation.

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Authors and Affiliations



L.B., C.F., A.N., J.F., S.H., M.G., C.H. and C.N.C. performed the experiments, interpreted the data and assisted with the paper. K.H. and R.M. provided essential materials and generated the SorA derivatives. W.-R.A. performed the 13C incorporation analysis. N.G. and E.P. performed the palmitoylation assay. A.S., H.B. and S.K.T. performed the metabolic analysis using HPLC–mass spectrometry or mass spectrometry. C.T.M and J.H. supported the work with key suggestions and helped with interpretation of the data. M.L. and T.S. designed the research, interpreted the data and wrote the paper.

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Correspondence to Matthias Lochner or Tim Sparwasser.

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The authors declare no competing financial interests.

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Supplementary Text and Figures

Supplementary Figures 1–14 and Supplementary Tables 1 and 2. (PDF 3852 kb)

Supplementary Table 3

Real-time PCR analysis of metabolic genes in wild-type and ACC1-deficient CD4+ T cells cultured under TH17 (DMSO/SorA/TACC1) or Treg inducing conditions (XLS 38 kb)

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Berod, L., Friedrich, C., Nandan, A. et al. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat Med 20, 1327–1333 (2014).

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