The Experimental Study Of NK Cell Receptors In Recently Diagnosed Type2Diabetes Mellitus Patients

Type2Diabetes Mellitus is one of the most common endocrine metabolicdiseases，Which has genetic predisposition, the environmental factors can leadto the disease.In recent years, with the increasing number of obesity and aging,in the United States, type2diabetes is rapidly becoming the most commonchronic disease, about1.5million new cases in each year[3].Diabetes is nowbecome the third largest non-communicable diseases,after the tumor andcardio-cerebrovascular disease, threatening people’s health.The pathogenicprocess of T2DM is not fully understood.A hypothesis was proposed toexplain the pathogenesis of T2DM by connecting the disease to a state ofpreclinical chronic inflammation that results from abnormalities in innateimmunity pathways[1,2].Natural killer (CD3-CD56+NK) cells are important components of theinnate system and they have the ability to both directly kill target cells and tointeract with antigen-presenting cells as well as with T cells.NK cells can beactivated and express activating receptors,such as NKG2D and naturalcytotoxicity receptors of NKp30,NKp44,NKp46,and others.NK cells canexpress inhibitory receptors,including the lectin-like CD94-NKG2Areceptors,and the killer cell immunoglobulin-like receptors (KIRs),such asKIR3DL1and KIR2DL3.Engagement of inhibitory receptors by humanleukocyte antigen (HLA) class I molecules initiates an inhibitory signal andinhibits the cytotoxicity of NK cells against the target cells.In addition,activated NK cells can produce inflammatory cytokines,such as IFN-γ anddegranulate granzyme and other cytotoxic factors,mediating cytotoxicityagainst target cells. Objective:Analysis of the relationship between peripheral blood activated andinhibitory NK cells and inducible IFN-γ and CD107a NK cells with the newcases of type2diabetes for provide a new method in treatment of type2diabetes in clinnical.Method:A total of16patients (Male9cases, female7cases)with new onset T2DMand9healthy(Male5cases,female4cases)subjects were recruited,and thefrequency of peripheralblood activated NK cell (NKG2C,NKG2D, NKp30,NKp44,NKp46)andinhibitory NK cell(KIR3DL1,KIR2DL3, NKG2A, CD158a,CD158b) in individual subjects was determined by flow cytometry. Thefrequency of spontaneous and inducible IFN-γ and CD107a NK cells wasfurther examined,and the potential association of the frequency of NK cellswith clinical measures was analyzed.Result:While there was no significant difference in the frequency of peripheralblood NK cell between patients and controls,the frequency of NKG2D NK cellsin patients was significantly higher than those in the controls (P=0.011).Incontrast,the frequency of NKG2A and KIR2DL3inhibitory NK cell in patientswas significantly lower than those in the controls (p=0.002,P<0.0001,respectively).Furthermore,the frequency of NKG2D NK cells was correlatedsignificantly with the values of BMI in patients.Moreover,the frequency ofspontaneous and inducible CD107a,but not IFN-γ-secreting NK cells in patientswere significantly higher than those in the controls (P=0.004,P<0.0001).Conclusion:Our data indicated that a higher frequency of activated NK cells and thelow frequency of inhibitory NK cells in patients with T2DM may reduce the threshold for the activation of NK,may participate in the pathogenesis ofT2DM.