Neuropilin-1 high monocytes protect against neonatal inflammation.
Xiaoqing ZhengWen LeiYongmei ZhangHan JinCha HanFan WuChonghong JiaRuihong ZengZhanghua ChenYuxia ZhangHaitao WangQiang LiuZhi YaoYing YuJie ZhouPublished in: Cellular & molecular immunology (2024)
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, yet the underlying mechanisms of which remain poorly understood. In this study, we identified a subset of neonatal monocytes characterized by high levels of neuropilin-1 (Nrp1), termed Nrp1 high monocytes. Compared with their Nrp1 low counterparts, Nrp1 high monocytes displayed potent immunosuppressive activity. Nrp1 deficiency in myeloid cells aggravated the severity of NEC, whereas adoptive transfer of Nrp1 high monocytes led to remission of NEC. Mechanistic studies showed that Nrp1, by 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 findings reveal an important immunosuppressive axis in neonatal monocytes and provide a potential therapeutic strategy for treating inflammatory disorders in neonates.
Keyphrases
- dendritic cells
- transcription factor
- peripheral blood
- oxidative stress
- nitric oxide
- early life
- low birth weight
- induced apoptosis
- bone marrow
- acute myeloid leukemia
- immune response
- nitric oxide synthase
- rheumatoid arthritis
- systemic lupus erythematosus
- cell death
- dna methylation
- mesenchymal stem cells
- reactive oxygen species
- ulcerative colitis
- drug induced
- genome wide
- high glucose
- stress induced
- replacement therapy