Study On The Function Of PirB In The Central Nervous System

Paired immunoglobulin receptor B,is an immunosuppressive receptor,and its corresponding homologue in human body is white blood immunoglobulin receptor B2(LILRB2),which is highly expressed in the nervous system.PirB protein is a type I transmembrane glycoprotein,not binding to other subunits.There are six immune globular domains outside the cell membrane.A structure containing an inhibitory motif based on immune receptor tyrosine(ITIM)was detected in the cells,which can recruit Src homologous region 2,including protein tyrosine phosphatase 1(SHP-1)or 2(SHP-2)leading to nerve regeneration inhibited.PirB is highly expressed in the injured central nervous system and acts as the second receptor of axonal growth inhibitor,which has the same function as Ng R.Because PirB promotes the occurrence and development of leukemia in the hematopoietic system,it is highly expressed as a matched immunoglobulin-like receptor in the hematopoietic system and is widely distributed in the injured nervous system.Therefore,this paper studied the effects of PirB on the proliferation and differentiation of neural stem cells in the central nervous system using PirB knockout mice whose nestin promoter region was inserted into GFP.By collecting mice of all ages(1M,2M,6M,12M),it was found that PirB knockout promoted neurogenesis.Subsequently,neural stem cells were isolated and cultured in vitro and it was found that PirB inhibited the proliferation and differentiation of neural stem cells.It was also detected that PirB knockout significantly promoted the proliferation and differentiation of neural stem cells during the development of mice in vivo.Then,through the establishment of Nestin-Cre system in mice,Tamoxifen induced neural stem cells to trace the trend of neural stem cells in vivo,using immunofluorescence co-staining Nestin(GFP)with proliferation and differentiation markers.The results showed that PirB knockout promoted the differentiation of NSCs into neuron(DCX)and astrocytes(GFAP),as well as promoted the proliferation of NSCs(Brd U).Then the CCI model of brain injury was established in Nestin-GFP mice.Immunofluorescence co-staining showed that PirB knockout promoted the proliferation and differentiation of NSCs after brain injury,suggesting that PirB inhibit nerve regeneration after CCI brain injury.In a word,PirB can inhibit the neurogenesis and neural regeneration of central nervous system by inhibiting the proliferation and differentiation of neural stem cells in vivo,which provides a basis for the further study of PirB and provides a clear direction and train of thought for its mechanism.At the same time,it provides a potential therapeutic target and basis for the treatment of nervous system diseases and brain injury diseases.In conclusion,PirB knockout not only promotes the proliferation and differentiation of NSCs in vitro,but also promotes neurogenesis during mouse development and the proliferation and differentiation of NSCs in hippocampus in vivo.From CCI model,it was found that PirB knockout could significantly promote the proliferation and differentiation of NSCs after brain injury.These results suggest that PirB can inhibit neurogenesis and nerve regeneration in vivo.The results of this study can provide a potential therapeutic target for the treatment of neurodegenerative diseases and brain injury diseases,but also provide a basis for further study of PirB,and provide a clear direction and ideas for its mechanism.