The Relationship Of TRAF6 And The Different Mature State Of Dendritic Cell

Objective: Rheumatoid Arthritis(RA) is a common chronic, destructive autoimmune disease that is characterized by the immune balance was break and humoral immune was hyperfunction. Dendritic cell(DC) was the strongest antigen presenting cell in the body and it was the unique cell to activate the initial T cells to induce positive immune response, mature DC was thought to play a key role in the pathogenesis of RA. Tumor necrosis factor receptor-associated factor 6(TRAF6) was the key molecule in the process of DC development, activation, and mature, we will study the relationship between TRAF6 and the different state of DC which may provide new drug targets for the treatment of RA in the furture. Methods: We used the Cytokines rm GM – CSF,rmIL – 4 co-culture with bone marrow cells of C57 mice to induce the marrow cells development into immature dendritic cell. Then the immature DC was divided into four groups which co-culture with rmGM-CSF、rmIL-4、TNF-?、LPS、FK506 cytokines to induce them into different mature state; the cell surface molecule CD80, CD86, MHC-II were used by flow cytometry instrument to detect; the secretion of IL-12 was tested by ELISA; RT-PCR and Western-blot were used to test the expression of mRNA-TRAF6 and protein-TRAF6, respectively. Results: We have successfully induced immature DC by co-culture the Cytokines rmGM – CSF,rmIL – 4 with bone marrow cells of C57 mice. The expression of the cell surface molecules(CD80、CD86、MHC-II) has significant statistical differences between the groups(P?0.05), compared to other groups, CD86 was significantly increased in D group. The secretion of IL-12 was increased followed with the level of mature of DC. The secretion of IL-12 was up to 10620.73?276.73 pg/ml in the D group which was obvious increased than other groups(P?0.01). The expression of the mRNA-TRAF6, in the D group, was significant higher than other groups(P<0.01), while there was no difference between B and C group. The secretion of the protein of TRAF6, in the D group, was obvious increased than the others(P<0.01), A group was the lowest in the four groups. Conclusions: The expression of the co-stimulatory molecules were increased followed with the mature state of DC and the secretion of IL-12, mRNA-TRAF6 and Protein-TRAF6 was positively with the maturity of DC. We conclude that TRAF6 play an important role in the development, differentiation and mature of DC.