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Neuropilin-1 high monocytes protect against neonatal inflammation

ABSTRACT: Neuropilin-1 high monocytes protect against neonatal inflammation

PROVIDER: PRJNA1097663 | ENA |

REPOSITORIES: ENA

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Neuropilin-1 high monocytes protect against neonatal inflammation

Project description:Neonates are susceptible to inflammatory disorders such as necrotizing enterocolitis (NEC) due to their immature immune system. The timely appearance of regulatory immune cells in early life contributes to the control of inflammation in neonates, the underlying mechanisms of which remain poorly understood. In this study, we identified a subset of neonatal monocytes characterized with high levels of neuropilin-1 (Nrp1), termed Nrp1 high monocytes. Nrp1high monocytes displayed potent immunosuppressive activity as compared with their Nrp1low counterpart. Nrp1 deficiency in myeloid cells aggravated the severity of NEC, whereas adoptive transfer of Nrp1 highmonocytes led to remission of NEC. Mechanistic studies showed that Nrp1, via binding to its ligand Sema4a, induced intracellular p38-MAPK/mTOR signaling and activated the transcription factor KLF4. KLF4 transactivated Nos2 and enhanced the production of nitric oxide (NO), a key mediator of immunosuppression in monocytes. These observations uncover an important immunosuppressive axis in neonatal monocytes and provide a potential therapeutic strategy for inflammatory disorders in neonates.

2024-04-12 | GSE263510 | GEO

Neuropilin-1+ vs. Neuropilin-1- CD8+ T cells from Plasmodium berghei ANKA-infected mice

Project description:Characterization of Neuropilin-1+ and Neuropilin-1- splenic CD8+ T cells from Plasmodium berghei ANKA-infected C57BL/6 mice

2022-12-31 | GSE199569 | GEO

Clostridium sporogenes-derived metabolites protect against colonic inflammation

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Periportal macrophages protect against commensal-driven liver inflammation

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Periportal macrophages protect against commensal-driven liver inflammation [spatial transcriptomics]

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Real-time quantitative PCR analysis of human neonatal and adult monocytes

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| PRJNA562568 | ENA

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Microglia protect against age-associated brain pathologies

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Neuropilin-1+ vs. Neuropilin-1- CD8+ T cells from Plasmodium berghei ANKA-infected mice

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Neuropilin-1 is Required for the Suppressive Function of Human Regulatory T Cells

Project description:Regulatory T cells (Tregs), lymphocytes that suppress immunological reactions, are of great interest for our comprehension of homeostasis and regulation in the immune system and as a therapeutic target in the treatment of both immune-mediated pathologies and reactivation of the immune response in patients with cancer. Understanding the molecular mechanisms by which these cells are regulated in respone to their environment will help to inform clinical strategies targeting Tregs. We hypothesised that Neuropilin-1, a transmembrane co-receptor for ligands of the semaphorin and growth factor families, promotes the suppressive function of human Tregs. Utilising in vitro lentivirus-mediated transduction with shRNA to knock down neuropilin-1 in primary human Tregs, we demonstrated that neuropilin-1 knockdown Tregs were severely impaired in their capacity to suppress cell proliferation in vitro and in their ability to prolong allograft survival in a humanised mouse model of transplantation. While neuropilin-1-KD Tregs exhibited no defects in survival, proliferation and activation upon stimulation in vitro, we hypothesised that loss of NRP1 expression would alter the global gene expression profile of human Tregs, revealing a NRP1-dependent Treg-associated transcriptional signature.

2019-01-01 | GSE106932 | GEO

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