IL-7 engages multiple mechanisms to overcome chronic viral infection and limit organ pathology.
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.
Pellegrini, M; Calzascia, T; Toe, JG; Preston, SP; Lin, AE; Elford, AR; Shahinian, A; Lang, PA; Lang, KS; Morre, M; Assouline, B; Lahl, K; Sparwasser, T; Tedder, TF; Paik, J-H; DePinho, RA; Basta, S; Ohashi, PS; Mak, TW
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