B7-H6 is a co-stimulatory molecule discoveried recently. B7-H6 is not expressed on normal cells, but specially expressed on tumor cells. It can also be expressed on antigen presenting cells (APC) by the induction. The B7-H6 expression can be downregulated by HDACi. NK cells can be activated to release TNFα and IFNγ through B7H6-NKp30 pathway. The B7-H6 molecules expressed on the cell surface can be shedded to form soluble molecules. In the meantime, the B7-H6/NKp30 pathway may be involved in the pathogenesis of primary Sjogren syndrome. B7-H6/NKp30 may become a new therapeutic target for tumor, inflammation and autoimmune diseases. This review discusses the B7-H6 and receptor sructure, the expression and significance of B7-H6, the function and regulating mechanism of B7-H6 and the soluble molecules of B7-H6.
Autoimmune Diseases ; B7 Antigens ; metabolism ; Down-Regulation ; Humans ; Inflammation ; Killer Cells, Natural ; metabolism ; Natural Cytotoxicity Triggering Receptor 3 ; metabolism ; Neoplasms

OBJECTIVETo explore the mechanism of NK cell dysfunction in patients with multiple myeloma (MM).

METHODSThe expression of inhibitory receptors (CD158a and CD158b) and activating receptors NKG2D and NCRs (NKp30, NKp44 and NKp46) on CD3-CD56+NK cell of 13 MM patients and 30 healthy controls were analyzed by flow cytometry. The concentration of soluble NKG2D ligands (MICA, MICB, ULBP1, ULBP2 and ULBP3) in serum was detected by enzyme- linked immunosorbent assay (ELISA), and the cytotoxicity of NK cell against MM cell line by flow cytometry.

RESULTSThere are no significant differences of percentage and absolute number of NK cells, and the expression level of CD158a and CD158b between MM patients and healthy individuals (P>0.05). No NKp44 expression was detected on fresh isolated NK cells from both groups. There is no difference in inhibitor receptors expression between MM patients and healthy individuals but the expression of NKG2D, NKp30 and NKp46 on NK cells were higher in MM patients as compared with that in healthy individuals. The concentration of soluble NKG2D ligands in serum was higher in MM patients as compared with that in healthy individuals (P<0.05). Cultured healthy individual's NK cells with MM patient's serum could significantly decrease its cytotoxicity against MM cell line U266 cells [(38.5 ± 6.5) % vs (25.4 ± 5.9)%, P=0.044］.

CONCLUSIONThe higher level of soluble NKG2D ligands in serum may be the mechanism of NK cell dysfunction in MM patient.

Cells, Cultured ; Flow Cytometry ; Humans ; Killer Cells, Natural ; metabolism ; pathology ; Multiple Myeloma ; immunology ; metabolism ; NK Cell Lectin-Like Receptor Subfamily K ; metabolism ; Natural Cytotoxicity Triggering Receptor 1 ; metabolism ; Natural Cytotoxicity Triggering Receptor 2 ; metabolism ; Natural Cytotoxicity Triggering Receptor 3 ; metabolism ; Receptors, KIR2DL1 ; metabolism ; Receptors, KIR2DL3 ; metabolism

Accumulating evidence has shown that allogeneic blood transfusions can induce significant immunosuppression in recipients, and thereby increase the risk of postoperative infection and/or tumor relapse. Although it is well known that natural killer (NK) cells are responsible for the immunodepression effects of transfusion, the underlying mechanisms remain obscure. In this study, we investigated the role of NK cells in transfusion-induced immunodepression in β-thalassemia major. The proportion of circulating NK cells and the expression of NK receptors (NKG2A, CD158a, NKP30, NKP46 and NKG2D) as well as CD107a were detected by multicolor flow cytometry. IFN-γ production by circulating NK cells was detected by intracellular cytokine staining. Our results showed that the proportion and cytotoxicity (CD107a expression) of circulating NK cells in transfusion-dependent β-thalassemia major patients were remarkably lower than those of β-thalassemia minor patients or healthy volunteers. Expression of NKG2A inhibitory receptor on circulating NK cells in patients with β-thalassemia major was remarkably up-regulated, but there were no significant differences in the expression levels of NKP30, NKP46, NKG2D, CD158a and IFN-γ. These results indicate NKG2A inhibitory receptor may play a key role in transfusion-induced immunodepression of NK cells in patients with β-thalassemia major.
Adolescent ; Child ; Female ; Flow Cytometry ; Gene Expression Regulation ; Humans ; Immunosuppression ; Killer Cells, Natural ; immunology ; metabolism ; Male ; NK Cell Lectin-Like Receptor Subfamily C ; blood ; immunology ; NK Cell Lectin-Like Receptor Subfamily K ; blood ; immunology ; Natural Cytotoxicity Triggering Receptor 1 ; blood ; immunology ; Natural Cytotoxicity Triggering Receptor 3 ; blood ; immunology ; Receptors, KIR2DL1 ; blood ; immunology ; Transfusion Reaction ; beta-Thalassemia ; blood ; immunology ; pathology