Editors' ChoiceImmunology

Starving T Cells

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Science Signaling  09 Jun 2009:
Vol. 2, Issue 74, pp. ec192
DOI: 10.1126/scisignal.274ec192

The TH17 lineage of CD4+ helper T cells, characterized by the ability to secrete IL-17, is an important mediator of inflammation and autoimmunity. Dampening the responses of these cells or inhibiting their differentiation is of great therapeutic interest. Sundrud et al. (see the Perspective by Blander and Amsen) now show that the small molecule halofuginone inhibits the differentiation of TH17 cells, but not other CD4+ T cell helper lineages, both in vitro and in a mouse model of multiple sclerosis. This selective inhibition was mediated by activation of the amino acid starvation response. Amino acid depletion mimicked the effects of halofuginone, whereas excess amino acids rescued TH17 differentiation. The results highlight the importance of amino acid metabolism in regulating inflammation.

M. S. Sundrud, S. B. Koralov, M. Feuerer, D. P. Calado, A. E. Kozhaya, A. Rhule-Smith, R. E. Lefebvre, D. Unutmaz, R. Mazitschek, H. Waldner, M. Whitman, T. Keller, A. Rao, Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science 324, 1334–1338 (2009). [Abstract] [Full Text]

J. M. Blander, D. Amsen, Amino acid addiction. Science 324, 1282–1283 (2009). [Summary] [Full Text]

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