No abstract

Xianyang city is one of the main hemorrhagic fever with renal syndrome (HFRS) epidemic areas in northwest China. Although the HFRS immunity program has been provided in this city, HFRS is still occurred every year. In order to implement the vaccination program effectively and to control HFRS, the analysis of antibody responses specific to Hantaan virus (HTNV) in individuals after vaccination is essential. In this study, a total of 100 subjects were divided into 5 groups: unvaccinated, 1, 3, 29 and 33 months after boost vaccination. The levels and the positive rates of HTNV-NP-specific IgM and IgG antibodies as well as HTNV neutralizing antibodies were significantly increased in the serum of the vaccinated individuals. The positive rates and levels of HTNV-NP-specific IgG and HTNV neutralizing antibody reached their highest values at 3 months respectively and could be sustained up to 33 months after vaccination. Moreover, the titres of HTNV-NP-specific IgM or IgG antibody and the titres of HTNV neutralizing antibody at 1 month after vaccination have a positive correlation. The level of HTNV-NP-specific IgG antibody was much higher than that of HTNV-NP-specific IgM antibody or HTNV neutralizing antibody. In addition, the strongest responses of antibody-secreting cells were observed at 3 months after vaccination, which was consistent with the serum results. Therefore, the HFRS immunization program is effective to induce humoral immunity in the population of northwest China.

Treatment targeting CD226 can ameliorate experimental autoimmune encephalomyelitis (EAE), the widely accepted model of MS. However, the mechanisms still need to be elucidated. Here we showed that CD226 blockage by anti-CD226 blocking mAb LeoA1 efficiently promoted IL-10 production in human peripheral blood monocytes (PBMC) or in mixed lymphocyte culture (MLC) system, significantly induced the CD4+IL-10+ T cell differentiation while suppressing the generation of Th1 and Th17. Furthermore, CD226 pAb administration in vivo reduced the onset of EAE in mice by promoting IL-10 production and regulating T cell differentiation. Concomitantly, the onset and severity of EAE were reduced and the serum IL-10 expression levels were increased in CD226 knockout mice than that in control mice when both received EAE induction. These novel findings confirmed that CD226 played a pivotal role in mediating autoimmune diseases such as EAE. Furthermore, to our knowledge, we show for the first time that IL-10 is an important contributor in the inhibitory effects of CD226 ligation on EAE.

The findings demonstrate that activating the Toll-like receptor-4 signaling pathway in HPDLFs using LPS triggers the UPR in vitro, warranting additional investigation into the precise mechanisms by which pathways promote this response under inflammatory conditions.

Cluster of differentiation 226 (CD226) molecules play a crucial role in the activation of effector CD4 + T cells during the immune response process, but a cell-intrinsic function of CD226 in CD4 + T subsets is not clear. In this study, we showed that Cd226 −/− mice were resistant to myelin oligodendrocyte glycoprotein peptide 35-55 (MOG 35−55)-induced experimental autoimmune encephalomyelitis (EAE) with highly expressed IL-10 + CD4 + T cells and downregulated IL-17A + CD4 + T cells when compared with wild-type (WT) mice. Th17 cell infiltration into the central nervous system (CNS) was largely decreased in the absence of CD226 during EAE. CD226 deficiency facilitated the proliferation of regulatory T cells (Tregs), with increased numbers of Tregs observed in EAE mice, and supported the elevated induced regulatory T cell (iTregs) proliferation in vitro. The Akt and Erk signaling pathways were shown to be involved in Cd226 −/− Treg proliferation and function in vivo and in vitro. These findings collectively indicate that CD226 is a key molecule regulating the Treg-mediated suppression of autoimmune responses by inhibiting Treg proliferation. Thus, the results of this study identify additional mechanisms by which CD226 regulates Treg functions in EAE and supports the potential therapeutic effects of anti-CD226 molecules on autoimmune diseases.