The Experimental Study Of NK Activating Receptors In Recently Diagnosed Type 2 Diabetes Mellitus Patients

Diabetes mellitus is characterized by an immune-mediated progressive destruction of the pancreaticβcells. Accord to recommendations of that commission diabetes experts of 1997 ADA and 1998 WHO, Diabetes mainly divided into type 1 diabetes mellitus(T1DM),type 2 diabetes mellitus(T2DM),genstational diabetes and other special type.Type 1 diabetes mellitus(T1DM) is characterized by an immuno-mediated progressive destruction of the pancreaticβcells.Although the precise mechanisms involved in its pathogenesis are still unclear, it is known that autoreactive T cells have a central role in the process. Due to the ability of NK cells to kill target cells as well as to interact with antigen-presenting and T cells, it has been suggested that they could be involved in one or multiple steps of the immune-mediated attack that leads to T1DM. More recently,the frequency and activation state of blood NK cells were also involved in different stages of human type 2 diabetes.NK cells act through the cytotoxic destruction of their target cells. Unlike cytolitic T lymphocytes, they exert their effector function without the need forprevious in vitro or in vivo activation. This characteristic makes themremarkably suited tomediate the first line of defence against pathogens, as part of the innate immune response. When activated, NK cells induce apoptosis of the target cells mainly through the exocytosis of perforin and granzyme. They also secrete pro-inflammatory cytokines such as interferon gamma (IFNg), tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage inflammatory protein 1αand 1β.NK cells recognize the target cells through specific molecules on the surface of these cells. These molecules may be either inadequately present or absent due to cell infection or its transformation. In the first situation, this could be due to non-self molecules encoded by pathogens or, alternatively, selfmolecules only expressed in a higher frequency in certain adverse conditions. The second scenario implies the absence of molecules normally present on the surface of the autologous cells, like MHC classⅠ. These alterations could render these cells susceptible to NK lysis.Generally, this second mechanism alone does not trigger cytotoxicity, unless it is combined to the anomalous expression of other molecules on the target cell surface. NK cell function depends on the balance of various signals from stimulatory and inhibitory receptors, as well as the expression of their corresponding ligands NKG2D and natural cytotoxicity receptors (NCRs) are the main NK activating receptors. NCRs (NKp30,NKp44, NKp46 and NKp80) are expressed exclusivelyin NK cells and belong to the superfamily of immunoglobulins. The NKG2D receptor is expressed by the majority of human NK cells, differently from the other NKG2 receptors, which are inhibitory and form dimers with the receptor CD94, the receptor NKG2D is a homodimer that recognizes a variety of ligandsinduced by stress, such as non-classic HLA class I molecules MICA and MICB. NKp46 expressed in the mature cell. NK is the key features of the casualties NK the receptors. NKp44 only expressed in the cell. when the body surface NK is a viral infection. NK cells ncrs the surface of the situation will change.A few small studies in the 80s and 90s have shown a reduction of the frequency of NK cells in the peripheral blood in patients with T1DM, especially in the ones with recent onset. On the other hand other studies performed at that time did not find any abnormality in the frequency of NK cells in the peripheral blood.Functional abnormalities have also been reported in NK cells of patients with T1DM. NK cells act through its surface stimulatory receptors of a molecule match with mica, induce infection, foreign bodies, the organization and the stability of a monitoring role.Ogasawara et al.in the study found that the NOD mouse of the surface of the receptors NK activate express and the corroded NK cells cells toxic and secrete IFN-γ. Rodacki et al.researchers discovered activation of expression of surface stimulatory receptors a decline and nothing to do with this change in T1DM. the research in the activation of the surface of the receptors send diabetics NK cells in the activation of the receptors (NKp30, NKp46, NKG2C和NKG2D) expression are increasing.Purpose:To observe the variances of NK cells and its surface stimulatory receptors of in diabetes patients,and to explore the role of NK cells in the pathogenesis of diabetes mellitus,in order to offer some ideas and means for the forecast,monitor and therapy of autoimmune diabetes. Materials and Methods:40 recent-onset diabetes mellitus patients from the patients admitted to the department of endocrinology in our hospital,30 healthy controls from health-check screening were included in the study.The expressing of surface stimulatory receptors(NKp30, NKp46, NKG2C和NKG2D) of NK cells were detected by flow cytometry.We compared and analyzed the variances of NK cells and its surface stimulatory receptors in diabetes mellitus patients. Results:The expressed surface stimulatory receptors NKp30 of NK cell increase in recent-onset diabetes mellitus, have remarkable significance (P<0.05);The expressed surface stimulatory receptors NKp46 of NK cell increase in recent-onset diabetes mellitus, have remarkable significance (P<0.05);The expressed surface stimulatory receptors NKG2C of NK cell increase in recent-onset diabetes mellitus, have remarkable significance (P<0.05);The expressed surface stimulatory receptors NKG2D of NK cell increase in recent-onset diabetes mellitus, have remarkable significance (P<0.05);The expressed surface stimulatory receptors of the recent-onset diabetes mellitus patients has no correlation with age,HbA1c and FBG(P>0.05).Conclusions:The expression of surface receptors of NK cell (NKp30, NKp46, NKG2C和NKG2D) increase in diabetes mellitus patients,which may play a role in the pathogenesis of diabetes mellitus patients, probably participated in the diabetes. In the cells of different algorithms NK is activated, developing, utilizing NK the activation and even the adoption and transfer NK individual immune cells, can be tolerated as diabetes immune to provide new methods of prevention.