mTOR limits the recruitment of CD11b+Gr1+Ly6Chigh myeloid-derived suppressor cells in protecting against murine immunological hepatic injury
| Autor: | Zhengguo Zhang, Jiongbo Liao, Yiwei Chu, Yun Lu, Yujing Bi, Huanrong Liu, Shan Yang, Xi Chen, Ruifu Yang, Yan Zhang, Hui Yang, Guangwei Liu |
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| Rok vydání: | 2014 |
| Předmět: |
Immunology
Cell Population Inflammation Context (language use) Biology Nitric Oxide Mice Immune system Cell Movement Immune Tolerance medicine Animals Antigens Ly Immunology and Allergy Myeloid Cells education PI3K/AKT/mTOR pathway Sirolimus education.field_of_study CD11b Antigen Liver Diseases TOR Serine-Threonine Kinases Cell migration Cell Biology medicine.anatomical_structure Cancer research Myeloid-derived Suppressor Cell Receptors Chemokine medicine.symptom Signal Transduction |
| Zdroj: | Journal of Leukocyte Biology. 95:961-970 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.0913473 |
| Popis: | The mTOR pathway integrates diverse environmental inputs, including immune signals and metabolic cues, to direct the innate and adaptive immune responses. MDSCs are a heterogeneous cell population that plays a crucial regulatory effect in immune-related diseases. However, whether mTOR signaling affects the functions of MDSCs remains largely unknown. Here, we show that mTOR signaling is a pivotal negative determinant of MDSC recruitment in IMH disease. In the context of IMH, inhibition of mTOR with rapamycin in CD11b+Gr1+ MDSCs mediates protection against IMH and serves as a functional, suppressive immune modulator that results in increased CD11b+Gr1+Ly6Chigh MDSC recruitment to inflammatory sites. In agreement with this, mTOR down-regulation promotes CD11b+Gr1+Ly6Chigh MDSC migration in vitro and in vivo. Mechanistically, mTOR activity down-regulation in MDSCs induced iNOS expression and NO production. Pharmacologic inhibition of iNOS completely eliminated MDSC recruitment. This study identifies MDSCs as an essential component for protection against IMH following rapamycin treatment. Rapamycin treatment or mTOR inhibition promotes CD11b+Gr1+Ly6Chigh MDSC recruitment and is critically required for protection against hepatic injury. This study further validates the targeting of mTOR signaling as a potential therapeutic approach to IMH-related diseases. |
| Databáze: | OpenAIRE |
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