Lawrence Steinman, MD

Publication Details

  • IL-7 Promotes T(H)1 Development and Serum IL-7 Predicts Clinical Response to Interferon-beta in Multiple Sclerosis SCIENCE TRANSLATIONAL MEDICINE Lee, L., Axtell, R., Tu, G. H., Logronio, K., Dilley, J., Yu, J., Rickert, M., Han, B., Evering, W., Walker, M. G., Shi, J., de Jong, B. A., Killestein, J., Polman, C. H., Steinman, L., Lin, J. C. 2011; 3 (93)

    Abstract:

    The interleukin-7 receptor ? chain (IL-7R?) 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 (T(H)1)-driven, but not a T(H)17-driven, form of MS exhibited a good clinical response to interferon-? (IFN-?) therapy. We now demonstrate that high serum levels of IL-7, particularly when paired with low levels of IL-17F, predict responsiveness to IFN-? and hence a T(H)1-driven subtype of MS. We also show that although IL-7 signaling is neither necessary nor sufficient for the induction or expansion of T(H)17 cells, IL-7 can greatly enhance both human and mouse T(H)1 cell differentiation. IL-7 alone is sufficient to induce human T(H)1 differentiation in the absence of IL-12 or other cytokines. Furthermore, targeting IL-7/IL-7R? is beneficial in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Mice treated with IL-7R?-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-7R? 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 T(H)1-driven form of MS and may predict outcome in MS patients undergoing IFN-? therapy. Blockade of IL-7 and the IL-7R? pathway may have therapeutic potential in MS and other autoimmune diseases.

    View details for DOI 10.1126/scitranslmed.3002400

    View details for Web of Science ID 000293170300004

    View details for PubMedID 21795588

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