@article{070ba91f4eec4627b9c5214d1f49874f,
title = "IL-7 engages multiple mechanisms to overcome chronic viral infection and limit organ pathology",
abstract = "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.",
author = "Marc Pellegrini and Thomas Calzascia and Toe, {Jesse G.} and Preston, {Simon P.} and Lin, {Amy E.} and Elford, {Alisha R.} and Arda Shahinian and Lang, {Philipp A.} and Lang, {Karl S.} and Michel Morre and Brigitte Assouline and Katharina Lahl and Tim Sparwasser and Tedder, {Thomas F.} and Paik, {Ji Hye} and DePinho, {Ronald A.} and Sameh Basta and Ohashi, {Pamela S.} and Mak, {Tak W.}",
note = "Funding Information: Dr. Mandana Nikpour assisted with statistical analyses. Marina Zaitseva contributed to the analysis of thymic emigrants; Alain Lamarre, Paul Jolicoeur, and Michel Nussenzweig provided reagents and mice. This work was supported by a Canadian Institute for Health Research grant to T.W.M. and P.S.O. (CIHR-MOP-106529) and a Terry Fox Cancer Foundation National Cancer Institute of Canada grant to T.W.M. T.C. was supported by the Boninchi Foundation (Geneva, Switzerland) and The Terry Fox Foundation through an award from the National Cancer Institute of Canada. M.P. was supported through an Irvington Institute Fellowship with the Cancer Research Institute (New York, NY) and an Australian National Health and Medical Research Council Fellowship. S.B receives support from the Natural Sciences and Engineering Research Council of Canada. P.S.O. holds a Canada Research Chair in autoimmunity and tumor immunity. This research was also funded, in part, by the Ontario Ministry of Health and Long Term Care (OMOHLTC). The views expressed do not necessarily reflect those of the OMOHLTC. ",
year = "2011",
month = feb,
day = "18",
doi = "10.1016/j.cell.2011.01.011",
language = "English (US)",
volume = "144",
pages = "601--613",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}