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

被引：322

作者：

Pellegrini, Marc ^{[1
,2
,3
,4
]}

Calzascia, Thomas ^{[1
,2
]}

Toe, Jesse G. ^{[3
]}

Preston, Simon P. ^{[3
]}

Lin, Amy E. ^{[1
,2
]}

Elford, Alisha R. ^{[1
,2
]}

Shahinian, Arda ^{[1
,2
]}

Lang, Philipp A. ^{[1
,2
]}

Lang, Karl S. ^{[1
,2
]}

Morre, Michel ^{[5
]}

Assouline, Brigitte ^{[5
]}

Lahl, Katharina ^{[6
]}

Sparwasser, Tim ^{[7
]}

Tedder, Thomas F. ^{[8
]}

Paik, Ji-hye ^{[9
,10
]}

DePinho, Ronald A. ^{[9
,10
]}

Basta, Sameh ^{[11
]}

Ohashi, Pamela S. ^{[1
,2
]}

Mak, Tak W. ^{[1
,2
]}

机构：

[1] Univ Hlth Network, Dept Med Biophys, Campbell Family Canc Res Inst, Ontario Canc Inst, Toronto, ON M5G 2C1, Canada

[2] Univ Hlth Network, Dept Immunol, Campbell Family Canc Res Inst, Ontario Canc Inst, Toronto, ON M5G 2C1, Canada

[3] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3052, Australia

[4] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3050, Australia

[5] Cytheris Inc, F-92130 Issy Les Moulineaux, France

[6] Stanford Univ, Lab Immunol & Vasc Biol, Dept Pathol, Sch Med, Stanford, CA 94305 USA

[7] Ctr Expt & Clin Infect Res, Inst Infect Immunol, TWINCORE, D-30625 Hannover, Germany

[8] Duke Univ, Dept Immunol, Med Ctr, Durham, NC 27708 USA

[9] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Dept Med Oncol,Dept Med,Dana Farber Canc Inst, Boston, MA 02115 USA

[10] Harvard Univ, Sch Med, Dept Genet, Dana Farber Canc Inst, Boston, MA 02115 USA

[11] Queens Univ, Dept Microbiol & Immunol, Kingston, ON K7L 396, Canada

来源：

CELL | 2011年 / 144卷 / 04期

基金：

英国医学研究理事会; 加拿大自然科学与工程研究理事会;

关键词：

CD4(+) T-CELLS; IN-VIVO; LYMPHOID-TISSUE; HOST-DEFENSE; INTERLEUKIN-22; ACTIVATION; EXPANSION; INFLAMMATION; PERSISTENCE; HEPATOCYTES;

D O I：

10.1016/j.cell.2011.01.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 down-regulated 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.

引用

页码：601 / 613

页数：13

共 48 条

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IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia [J].