Introduction of the two-way regulation of CD69

Is a type of transmembrane glycoprotein consisting of 199 amino acids, including a 40-residue intracellular region, a 21-residue transmembrane region, and a 138-residue extracellular region with characteristic Ca2+ The conformation glycosyl recognition region CD69 is usually present as a homodimer, and is linked by two disulfide bonds of two chains having a molecular weight of 28 kD and 32 kD, which are passed through different glycosyl groups of a polypeptide chain having a molecular weight of 22.5 kD. Composition.

Since CD69 was discovered, its initial study was essentially about its role in cell activation. CD69 can be expressed in almost all myeloid cells but in addition to persistent low levels of expression in platelets and monocytes, CD69 is in other The cells are not expressed at rest, but expression after cell activation is mainly focused on its expression in T cells and NK cells. The mechanism of CD69 expression is mainly the activation of PKC and the continuous increase of intracellular Ca2+ levels. Blocking the PKC pathway directly inhibits the expression of CD69. The rapid expression of CD69 in activated cells is not only a marker molecule. In fact, its more important role is to further enhance cell activation or proliferation as a cell costimulatory signal.

Although CD69 plays an important role in cell activation, recent studies have shown that the expression of CD69 is closely related to cell apoptosis in vivo. The T cells with high expression of CD69 activated in vivo are prone to rapid and spontaneous apoptosis in vitro. The survival rate of lymphocytes in the peritoneal and spleen of CD69-/- mice is increased, the apoptosis is significantly reduced, and the apoptosis of spleen lymphocytes is obvious after activation. Lower than wild-type mice, and there is a decrease in activation of the apoptotic signal caspase-3. It was found that Eos with high expression of CD69 after PMA stimulation also showed a significant increase in apoptosis; when human Eos was cultured in vitro, the addition of antiCD69mAb increased apoptosis, accompanied by anti-apoptotic signal B cell lymphoma/leukemia-2 (B -cell leukemia-lymphoma, bcl-2) reports of decreased expression, and Eos apoptosis induced by cross-linking of CD69 with antibodies is not affected by GM-CSF in the surrounding environment. The apoptotic cells that can be mediated by CD69 are mainly activated eosinophils and monocytes. The molecular mechanism of CD69-mediated apoptosis remains unclear. Studies have shown that CD69-mediated monocyte apoptosis is associated with three distinct signaling pathways: (1) dependent on NO; (2) and phospholipase A2/phospholipid oxidation The enzyme cascade is related; (3) is affected by pertussis toxin (PTX)-sensitive G protein, and all three are necessary and insufficient conditions for inducing apoptosis of mononuclear phagocytic cells.