CD49a Regulates The Function Of Human Decidual NK Cells

Backgrounds: Natural killer cells are one of important components in innate immune system,and also have important roles in regulating adaptive immune responses.Natural killer cells are large granular lymphocytes that develop from hematopoietic stem cell,In addition,It has been reported that NK cells may have a migratory capacity from peripheral blood to the decidua and acquire the unique functional features under the effect of decidual microenviroment factors.Unlike T cells or B cells,NK cells can exert cytotoxic effect by killing malignant,virus-infected cells and secreting a range of inflammatory cytokines without prior stimulation or activation and constitutes the first line of defense again the tumor and pathogens.During the early pregnancy,approximately 50%-90% of the decidual lymphocytes are NK cells,while the other immune cells are rare.Some reasearchers has showed a detailed feature of gene expression in the d NK cells(decidual NK cells),they are differ in CD56dimCD16+ and CD56brightCD16-p NK cells(Peripheral blood NK cell).DNK cells have higher cytokine secretion ability and lower killing effect than p K cell.At the same time,CD49 a is overexpressed in d NK cells subsets than that of p NK.As an special adhesion molecule,CD49 a can plays an important role in biological processes such as inflammation,innate immunity,cell adhesion,migration,growth and differentiation.Here,we found differently expression between d NK cells and d NK cells of recurrent spontaneous abortion patients(RSA).The expression of CD49 a in the d NK cells exceeded that of in RSA d NK.It have not been reported that there have some relationship between NK cells function and the higer expression about CD49 a in the d NK cells.we remain confused about the underlying molecular mechanisms about the phenomenon.Long noncoding RNA,is noncoding RNA that transcripts more than 200 nucleotides,and aslo play a critical roles in regulating the process of transcription and posttranscription of gene expression.Here,we identified the novel Lnc RNA,Lnc-49 a by Lnc RNA microarray that is overexpressed in human d NK cells subsets.In this reasearch,we mainly set out to research the influence of Lnc-49 a for the expression of CD49 a and human d NK cells functions.Research contents: 1.Highly purified human NK cells were isolated from PBMCs using the NK cell Isolation Kit.2.FACS analysis of the different expression about perforin,Granzyme-? and CD49 a between d NK and RSA d NK.3.Transwell and adhesion assay analysis for the expression of d NK migration and adhesion abilities by CD49 a neutralization.4.QPCR analysis for the expression of perforin,Granzyme-?,IFN-? in d NK by CD49 a neutralization.5.QPCR and FACS analysis for the expression of CD49 a and perforin,IFN-? when d NK cells was transfected with Lnc-49 a si RNA.6.Assay of NK cell cytotoxicity detected the d NK cells cytotoxicity when d NK cells was transfected with Lnc-49 a si RNA.Research results: 1.More than 90% pure NK cells were obtained by using magnetic beads.2.The expression of CD49 a in d NK cell exceeded that of in RSA d NK.Perforin,Granzyme-? is overexpressed in RSA d NK cells than d NK cell.3.The d NK cell migration and adhesion ability were inhibited significantly by CD49 a neutralization.4.The expression of perforin,Granzyme-?,IFN-? was increased in d NK cell by CD49 a neutralization.5.Lnc-49 a si RNA significantly inhibited the expression of CD49 a and promoted the expression of perforin,IFN-? and the cytotoxicity ability in d NK cells.Conclusion: 1.CD49 a can promote the migration and adhesion ability of d NK cell and inhibite the expression of perforin,Granzyme-B,IFN-r.2.Lnc-49 a positively regulates CD49 a and inhibited the expression of perforin,IFN-? in d NK cell.