Neutrophils Confer T Cell Resistance to Myeloid-Derived Suppressor Cell-Mediated Suppression To Promote Chronic Inflammation

被引:13
作者
Ryan, Sean O. [1 ]
Johnson, Jenny L. [1 ]
Cobb, Brian A. [1 ]
机构
[1] Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA
基金
美国国家卫生研究院;
关键词
CHRONIC GRANULOMATOUS-DISEASE; NITRIC-OXIDE; INTERLEUKIN-10-DEFICIENT MICE; POLYMORPHONUCLEAR NEUTROPHILS; INTERFERON-GAMMA; BOWEL-DISEASE; RESPONSES; MACROPHAGES; IL-10; POLYMORPHISM;
D O I
10.4049/jimmunol.1203404
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Low-grade chronic inflammation can persist in aging humans unnoticed for years or even decades, inflicting continuous damage that can culminate later in life as organ dysfunction, physical frailty, and some of the most prominent debilitating and deadly age-associated diseases, including rheumatoid arthritis, diabetes, heart disease, and cancer. Despite the near universal acceptance of these associations, the mechanisms underlying unresolved inflammation remain poorly understood. In this study, we describe a novel inducible method to examine systemic chronic inflammation using susceptible animal models. Induced inflammation results in unresolved innate cellular responses and persistence of the same serum proinflammatory molecules used as diagnostic biomarkers and therapeutic targets for chronic inflammation in humans. Surprisingly, we found long-term persistence of an inflammation-associated neutrophil cell population constitutively producing the proinflammatory IFN-gamma cytokine, which until now has only been detected transiently in acute inflammatory responses. Interestingly, these cells appear to confer T cell resistance to the otherwise potent anti-inflammatory function of myeloid-derived suppressor cells, revealing a novel mechanism for the maintenance of chronic inflammatory responses over time. This discovery represents an attractive target to resolve inflammation and prevent the inflammation-induced pathologies that are of critical concern for the well-being of the aging population.
引用
收藏
页码:5037 / 5047
页数:11
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