| RRC ID |
48266
|
| 著者 |
Masamoto Y, Arai S, Sato T, Yoshimi A, Kubota N, Takamoto I, Iwakura Y, Yoshimura A, Kadowaki T, Kurokawa M.
|
| タイトル |
Adiponectin Enhances Antibacterial Activity of Hematopoietic Cells by Suppressing Bone Marrow Inflammation.
|
| ジャーナル |
Immunity
|
| Abstract |
Obesity has been shown to increase the morbidity of infections, however, the underlying mechanisms remain largely unknown. Here we demonstrate that obesity caused adiponectin deficiency in the bone marrow (BM), which led to an inflamed BM characterized by increased tumor necrosis factor (TNF) production from bone marrow macrophages. Hematopoietic stem and progenitor cells (HSPCs) chronically exposed to excessive TNF in obese marrow aberrantly expressed cytokine signaling suppressor SOCS3, impairing JAK-STAT mediated signal transduction and cytokine-driven cell proliferation. Accordingly, both obese and adiponectin-deficient mice showed attenuated clearance of infected Listeria monocytogenes, indicating that obesity or loss of adiponectin is critical for exacerbation of infection. Adiponectin treatment restored the defective HSPC proliferation and bacterial clearance of obese and adiponectin-deficient mice, affirming the importance of adiponectin against infection. Taken together, our findings demonstrate that obesity impairs hematopoietic response against infections through a TNF-SOCS3-STAT3 axis, highlighting adiponectin as a legitimate target against obesity-related infections.
|
| 巻・号 |
44(6)
|
| ページ |
1422-33
|
| 公開日 |
2016-6-21
|
| DOI |
10.1016/j.immuni.2016.05.010
|
| PII |
S1074-7613(16)30198-4
|
| PMID |
27317261
|
| MeSH |
Adiponectin / genetics
Adiponectin / metabolism*
Animals
Bacteriolysis
Bone Marrow / immunology
Cells, Cultured
Diet
Gene Expression Regulation
Hematopoiesis
Hematopoietic Stem Cell Mobilization
Hematopoietic Stem Cells / physiology*
Inflammation / immunology*
Listeria monocytogenes / immunology*
Listeriosis / immunology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity / immunology*
Signal Transduction
Suppressor of Cytokine Signaling 3 Protein / genetics
Suppressor of Cytokine Signaling 3 Protein / metabolism
Tumor Necrosis Factor-alpha / metabolism
|
| IF |
22.553
|
| 引用数 |
18
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 一般微生物 |
JCM 7671 |
