C-relictive ProteinShapes The Global Adaptive Immune Responses By Direct Modulation Of T Cell Differentiation

When the body has inflamation and tissue damage, C-reactive protein has a shap rise in the plasma, as a acute protein and a nonspecific signs of inflammation in clinical practice. CRP is one of the earliest protective mechanisms in the body. For a long time, CRP is deemed to be a kind of soluble pattern recognition molecule, having an important function in host defense and preventing pathogens invasion, so CRP plays an important function in the innate immune system. CRP can recogenize the forigen antigens and autoantigene by the Fc gamma receptores of monocytes and macrophages, promoting the removal of pathogens as a scavenger; at the same time, CRP can active the classic complement system, but not form the membrane attack complex, thus has a opsonic action to the immune system. Therefore, CRP is a key molecule in the innate immune system, mainly participating in the innate immune response.In recent years, it is found that the functions of CRP not only perform in innate immune system, but also have a certain role in the acquired immune response from the study of CRP with cardiovascular disease like atherosclerosis and autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. Especially in 2002-2007, some researchers showed that a single injection of CRP or CRPtg mouse suffering from spontaneous and evoked autoimmune diseases such as EAE and SLE, can reverse the disease, with making the mice live longer. And what is more, the single inhection will be effective before or after the diseases occuring. However, studies on these animal models were just only by assessing the changes of diseases, as for, who has a direct interaction with injected CRP in vivo, a direct way or an indirect way of CRP to influence the acquired immune, there is no exact result.To discover the function of CRP in acquired immunity is our main target. Firstly, it is found that CRP can bind a surface receptor of Jurkat T cell and Mouse Naive T cell, which was confirmed by the flow cytometry and immunofluorescence. The combination do not dependent on the traditional CRP receptors, is insensitive to calcium ions and PC, can be eliminated by digesting of trypsin and proteinase k, which is proved by EDTA/PC elution and enzyme digestion, so a new receptor may exist. Secondly, The result shows that CRP can change the ability of cytokine secretion detected by real time PCR and cytokine ELISA, characterized by IL-4 up-regulation and IFN-gamma down-regulation, and then it is speculated that CRP may affect Th differentiation directly. Then it is confirmed that CRP can balance Thl/Th2 differentiation by FCM at a single cell level. Thirdly, the molecular mechanism which is involved in Th1/Th2 differentiation is discussed by detecting the expression of T-bet, GATA-3, p-STAT-1, p-STAT-4 and p-STAT-6. And then it is found that IL-2/IL-2R signals may be involved in the response of CRP and Th1/Th2 differentiation. Finally, in the EAE model experiment, it is found that a single injection of CRP and CRPtg mouse can alleviate the EAE disease significantly in vivo, with a Thl suppressing and Th2 promoting. So we proved CRP can reverse the mouse disease by modulating the Thl/Th2 balance, which can provide a theoretical guidance for control and treatment of some autoimmune disease.