IL-7 Engages Multiple Mechanisms to Overcome Chronic Viral Infection and Limit Organ Pathology

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• 作者：Marc Pellegrini¹ ; ² ; ³ ; ¹⁰ ; Thomas Calzascia³ ; ¹⁰ ; Jesse G. Toe¹ ; Simon P. Preston¹ ; Amy E. Lin³ ; Alisha R. Elford³ ; Arda Shahinian³ ; Philipp A. Lang³ ; Karl S. Lang³ ; Michel Morre⁴ ; Brigitte Assouline⁴ ; Katharina Lahl⁵ ; Tim Sparwasser⁶ ; Thomas F. Tedder⁷ ; Ji-hye Paik⁸ ; Ronald A. DePinho⁸ ; Sameh Basta⁹ ; Pamela S. Ohashi³ ; ¹¹ ; ^{pohashi@uhnres.utoronto.ca} ; Tak W. Mak³ ; ¹¹
• 刊名：Cell
• 出版年：2011
• 出版时间：18 February 2011
• 年：2011
• 卷：144
• 期：4
• 页码：601-613
• 全文大小：2203 K

文摘

Summary

Understanding the factors that impede immune responses to persistent viruses is essential in designing therapies for HIV infection. Mice infected with LCMV clone-13 have persistent high-level viremia and a dysfunctional immune response. Interleukin-7, a cytokine that is critical for immune development and homeostasis, was used here to promote immunity toward clone-13, enabling elucidation of the inhibitory pathways underlying impaired antiviral immune response. Mechanistically, IL-7 downregulated a critical repressor of cytokine signaling, Socs3, resulting in amplified cytokine production, increased T cell effector function and numbers, and viral clearance. IL-7 enhanced thymic output to expand the naive T cell pool, including T cells that were not LCMV specific. Additionally, IL-7 promoted production of cytoprotective IL-22 that abrogated liver pathology. The IL-7-mediated effects were dependent on endogenous IL-6. These attributes of IL-7 have profound implications for its use as a therapeutic in the treatment of chronic viral diseases.