FcγRⅡB修飾的樹突狀細(xì)胞預(yù)防和治療SLE小鼠.pdf

1、Dendritic cells (DCs) have been shown to be able to downregulate immune response, depending on their immature state or tolerogenic/regulatory subsets.The functions of DCs are controlled by a balance of the inhibitory and

2、 activating signals transduced through distinct surface receptors, and preferential expression of inhibitory receptors on DCs can negatively regulateantigen-presentation and cytokine production by DC. Inhibitory receptor

3、-FcyR Ⅱ B play a protective role in the development of autoimmune diseases.Immune complexes (Ics) accumulated in the circulation of lupus not only area major factor in pathological injuries, but also contribute to excess

4、 activationof immune responses to self-antigens by ligation of predominantly expressedactivating FcyRs.Therefore, the primary aim of this study is to investigate whether FcyRⅡ Boverexpressed in immature DC can enhance th

5、e tolerogenecity of immatureDC, especially in the presence of IC, thus leading to the attenuation of the lupus progression by infusion with FcyRⅡ B-overexpressing DC (DC-FcyRⅡB). We found that DC-FcyRⅡB displayed the pro

6、perties of immature DCs,illustrated by expressing moderate levels of costimulatory molecules-CD40,CD80, and CD86, and MHC-Ⅱand by secreting Iow levels of proinflammatory cytokines-TNF-α and IL-1β and large amounts of inh

7、ibitoryfactor-PGE2 upon exposure to IC. These IC-treated DC-FcyR!!B induced hyporesponses of T cells and mediated inhibitory effects on the OVA-specificT cells responses to mature and activated DCs partially dependent on

8、 PGE2production. Moreover, we found that DC-FcyRⅡB obviously prolonged the survival of MRL/Ipr, reduced the generation of serum autoantibodies specificfor DNA or chromatin and the Ics deposition in kidney, and ameliorate

9、d ofkidney pathological injury. Our results demonstrated that inhibitory FcyRⅡB-modified overexpressing DCs can downregulate immune response and infusion with FcyR Ⅱ B-overexpressing DCs may be used as a noveltherapeutic