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您的检索式：作者名="Steven X.Hou"
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| 1 | A neuron-immune circuit regulates neurodegeneration in the hindbrain and spinal cord of Arf1-ablated mice显示文摘Neuroimmune connections have been revealed to play a central role in neurodegenerative diseases(NDs).However,the mechanisms that link the central nervous system(CNS)and peripheral immune cells are still mostly unknown.We recently found that specific ablation of the Arf1 gene in hindbrain and spinal cord neurons promoted NDs through activating the NLRP3 inflammasome in microglia via peroxided lipids and adenosine triphosphate(ATP)releasing.Here,we demonstrate that IL-1βwith elevated chemokines in the neuronal Arf1-ablated mouse hindbrain and spinal cord recruited and activatedγδT cells in meninges.The activatedγδT cells then secreted IFN-γthat entered into parenchyma to activate the microglia-A1astrocyte-C3-neuronal C3a R neurotoxic pathway.Remarkably,the neurodegenerative phenotypes of the neuronal Arf1-ablated mice were strongly ameliorated by IFN-γor C3 knockout.Finally,we show that the Arf1-reduction-induced neuroimmune-IFN-γ-gliosis pathway exists in human NDs,particularly in amyotrophic lateral sclerosis and multiple sclerosis.Together,our results uncover a previously unknown mechanism that links the CNS and peripheral immune cells to promote neurodegeneration. | Guohao Wang Shuhan Jin Jiaqi Liu Xu Li Peng Dai Yuetong Wang Steven X.Hou | 2023 | National Science Review2023，10，12： | 0 |
| 2 | Blockade of Arf1-mediated lipid metabolism in cancers promotes tumor infiltration of cytotoxic T cells via the LPE-PPARγ-NF-κB-CCL5 pathway显示文摘Tumor immunotherapy has achieved breakthroughs in a variety of tumors. However, the systemic absence of T cells in tumors and immunosuppressive tumor microenvironment so far limits the efficacy of immunotherapy to a small population of patients. Therefore, novel agents to increase T-cell tumor infiltration are urgently needed in the clinic. We recently found that inhibition of the ADP-ribosylation factor 1 (Arf1)-mediated lipid metabolism not only kills cancer stem cells (CSCs) but also elicits an anti-tumor immune response. In this study, we revealed a mechanism that targeting Arf1 promotes the infiltration of cytotoxic T lymphocytes (CTLs) into tumors through the C-C chemokine ligand 5 (CCL5)- C-C chemokine receptor type 5 (CCR5) pathway. We found that blockage of Arf1 induces the production of the unsaturated fatty acid (PE 18:1) that binds and sequestrates peroxisome proliferator- activated receptor-γ (PPARγ) from the PPARγ-nuclear factor-κB (NF-κB) cytoplasmic complex. The released NF-κB was then phospho-rylated and translocated into the nucleus to regulate the transcription of chemokine CCL5. CCL5 promoted infiltration of CTLs for tumor regression. Furthermore, the combination of the Arf1 inhibitor and programmed cell death protein 1 (PD-1) blockade induced an even stronger anti-tumor immunity. Therefore, targeting Arf1 represents a novel anti-tumor immune approach by provoking T-cell tumor infiltration and may provide a new strategy for tumor immunotherapy. | Na Wang Tiange Yao Chenfei Luo Ling Sun Yuetong Wang Steven X.Hou | 2023 | Life Metabolism2023，2，5： | 0 |
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