IL-7 engages multiple mechanisms to overcome chronic viral infection and limit organ pathology.
Cell
; 144(4): 601-13, 2011 Feb 18.
Article
en En
| MEDLINE
| ID: mdl-21295337
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Interleucina-7
/
Coriomeningitis Linfocítica
/
Virus de la Coriomeningitis Linfocítica
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Año:
2011
Tipo del documento:
Article
País de afiliación:
Australia