| First Author | Cohen M | Year | 2014 |
| Journal | EMBO J | Volume | 33 |
| Issue | 24 | Pages | 2906-21 |
| PubMed ID | 25385836 | Mgi Jnum | J:216281 |
| Mgi Id | MGI:5608600 | Doi | 10.15252/embj.201489293 |
| Citation | Cohen M, et al. (2014) Chronic exposure to TGFbeta1 regulates myeloid cell inflammatory response in an IRF7-dependent manner. EMBO J 33(24):2906-21 |
| abstractText | Tissue microenvironment influences the function of resident and infiltrating myeloid-derived cells. In the central nervous system (CNS), resident microglia and freshly recruited infiltrating monocyte-derived macrophages (mo-MPhi) display distinct activities under pathological conditions, yet little is known about the microenvironment-derived molecular mechanism that regulates these differences. Here, we demonstrate that long exposure to transforming growth factor-beta1 (TGFbeta1) impaired the ability of myeloid cells to acquire a resolving anti-inflammatory phenotype. Using genome-wide expression analysis and chromatin immunoprecipitation followed by next-generation sequencing, we show that the capacity to undergo pro- to anti-inflammatory (M1-to-M2) phenotype switch is controlled by the transcription factor interferon regulatory factor 7 (IRF7) that is down-regulated by the TGFbeta1 pathway. RNAi-mediated perturbation of Irf7 inhibited the M1-to-M2 switch, while IFNbeta1 (an IRF7 pathway activator) restored it. In vivo induction of Irf7 expression in microglia, following spinal cord injury, reduced their pro-inflammatory activity. These results highlight the key role of tissue-specific environmental factors in determining the fate of resident myeloid-derived cells under both physiological and pathological conditions. |
