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Abstract
The interleukin-7 receptor α chain (IL-7Rα) gene was identified as a top non–major histocompatibility complex–linked risk locus for multiple sclerosis (MS). Recently, we showed that a T helper 1 (TH1)–driven, but not a TH17-driven, form of MS exhibited a good clinical response to interferon-β (IFN-β) therapy. We now demonstrate that high serum levels of IL-7, particularly when paired with low levels of IL-17F, predict responsiveness to IFN-β and hence a TH1-driven subtype of MS. We also show that although IL-7 signaling is neither necessary nor sufficient for the induction or expansion of TH17 cells, IL-7 can greatly enhance both human and mouse TH1 cell differentiation. IL-7 alone is sufficient to induce human TH1 differentiation in the absence of IL-12 or other cytokines. Furthermore, targeting IL-7/IL-7Rα is beneficial in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Mice treated with IL-7Rα–blocking antibodies before or after onset of paralysis exhibited reduced clinical signs of EAE, with reduction in peripheral naïve and activated T cells, whereas central memory T, regulatory T, B, and natural killer cell populations were largely spared. IL-7Rα antibody treatment markedly reduced lymphocyte infiltration into the central nervous system in mice with EAE. Thus, a serum profile of high IL-7 may signify a TH1-driven form of MS and may predict outcome in MS patients undergoing IFN-β therapy. Blockade of IL-7 and the IL-7Rα pathway may have therapeutic potential in MS and other autoimmune diseases.
Footnotes
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↵* These authors contributed equally to this work.
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Citation: L.-F. Lee, R. Axtell, G. H. Tu, K. Logronio, J. Dilley, J. Yu, M. Rickert, B. Han, W. Evering, M. G. Walker, J. Shi, B. A. de Jong, J. Killestein, C. H. Polman, L. Steinman, J. C. Lin, IL-7 Promotes TH1 Development and Serum IL-7 Predicts Clinical Response to Interferon-β in Multiple Sclerosis. Sci. Transl. Med. 3, 93ra68 (2011).
- Copyright © 2011, American Association for the Advancement of Science
