Research ArticleMultiple Sclerosis

IL-7 Promotes TH1 Development and Serum IL-7 Predicts Clinical Response to Interferon-β in Multiple Sclerosis

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Science Translational Medicine  27 Jul 2011:
Vol. 3, Issue 93, pp. 93ra68
DOI: 10.1126/scitranslmed.3002400

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An Expanding View of IL-7 in Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease characterized by loss of the myelin sheath protecting nerves, resulting in a variety of neurological symptoms including paralysis. Several genome-wide association studies have identified a variation (single-nucleotide polymorphism) in the gene encoding interleukin-7 receptor α (IL-7Rα), suggesting that this receptor may be associated with susceptibility to developing MS. Signaling via the IL-7R is necessary for the proliferation and survival of T lymphocytes. Now, Lee et al. investigate the role of IL-7 and its receptor on different T cell populations in MS. They show that IL-7 promotes the differentiation of human and mouse naïve T cells into T helper type 1 (TH1) cells but not TH17 cells. Both of these T helper cell populations are involved in the inflammatory response in MS. When the authors administered IL-7 to mice with experimental autoimmune encephalomyelitis (a mouse model of MS), disease symptoms were exacerbated. However, when they administered antibodies that blocked signaling via the IL-7Rα receptor, there was amelioration of disease symptoms even when antibodies were given after the onset of paralysis. The authors propose that blocking IL-7 or IL-7Rα may be a potential therapeutic strategy for treating MS driven by TH1 cells. Next, the authors wondered whether the IL-7 concentration in the serum of MS patients might be a useful indicator of whether the patients had MS driven by TH1 or TH17 cells. The authors demonstrate that high serum IL-7 concentrations correlate with MS driven by TH1 cells. To be able to identify MS patients with a TH1 or TH17 form of the disease is important because interferon-β (IFN-β) therapy given to patients with a TH1 form of MS improves symptoms, whereas IFN-β therapy given to patients with a TH17 form of the disease exacerbates symptoms. The authors go on to show that high IL-7 serum concentrations in MS patients indeed do correlate with a good clinical response of those MS patients to IFN-β therapy. Together, these data confirm the importance of IL-7 in TH1-driven MS and suggest that high serum concentrations of IL-7 could be used as a marker to identify MS patients with TH1-driven MS, who would benefit from IFN-β therapy.

Footnotes

  • * These authors contributed equally to this work.

  • 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).

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