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Osteopontin promotes dendritic cell maturation and function in response to HBV antigens.

Cui G, Chen J, He J, Lu C, Wei Y, Wang L, Xu X, Li L, Uede T, Diao H - Drug Des Devel Ther (2015)

Bottom Line: OPN secreted by DCs was compared.We found that OPN production of DCs from CHB patients was significantly lower than those from healthy volunteers.These findings suggested that OPN could improve the maturation and functioning of DCs in the immune response to HBV antigens, which might be useful to further improve the effect of DC vaccine.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China ; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, People's Republic of China.

ABSTRACT

Purpose: Dendritic cells (DCs) play critical roles in promoting innate and adaptive immunity in microbial infection. Functional impairment of DCs may mediate the suppression of viral-specific T-cell immune response in chronic hepatitis B (CHB) patients. Osteopontin (OPN) is involved in several liver diseases and infectious diseases. However, whether OPN affects DC function in hepatitis B virus (HBV) infection is unknown.

Methods: Twenty CHB patients and 20 healthy volunteers were recruited. OPN secreted by DCs was compared. Peripheral blood mononuclear cells cultured with OPN antibody were examined to study the costimulatory molecular expression and interleukin (IL)-12 production of DCs after HBV antigenic stimulation. OPN-deficient mice were used to investigate the influence of OPN on DC maturation and function after HBV antigenic stimulation in vitro and in vivo. Exogenous OPN was administrated to further verify the functioning of DCs from CHB patients upon HBV antigenic stimulation.

Results: We found that OPN production of DCs from CHB patients was significantly lower than those from healthy volunteers. The absence of OPN impaired IL-12 production and costimulatory molecular expression of DCs upon stimulation with HBV antigens. Defective DC function led to reduced activation of Th1 response to HBV antigens. In addition, OPN deficiency in DCs reduced the HBV antigen-induced inflammatory response in the liver of mice. Importantly, OPN administration significantly promoted the maturation of DCs from CHB patients in vitro.

Conclusion: These findings suggested that OPN could improve the maturation and functioning of DCs in the immune response to HBV antigens, which might be useful to further improve the effect of DC vaccine.

No MeSH data available.


Related in: MedlinePlus

OPN deficiency impaired the induction of polarized Th1 responses to HBV antigens through DCs.Notes: T-cells were isolated from the WT and OPN−/− mice spleen by MACS and cocultured with CD11c+ cells isolated from the cell derived from murine BM of WT mice and OPN−/− mice after HBV antigenic stimulations at a ratio of 10:1, respectively, and then cytokines levels in the coculture supernatants were detected by ELISA. The levels of IFN-γ (A), TNF-α (B), IL-4 (C) and IL-10 (D) in the coculture supernatants are compared. *P<0.05; **P<0.01. ***P<0.001.Abbreviations: OPN, osteopontin; DCs, dendritic cells; HBV, hepatitis B virus; BM, bone marrow; WT, wild-type; MACS, magnetically activated cell sorting; HBcAg, hepatitis B core antigen; HBsAg, surface antigen of the hepatitis B virus; IL, interleukin; TNF, tumor necrosis factor; IFN, interferon; BMDC, bone marrow-derived dendritic cell; ELISA, enzyme-linked immunosorbent assay.
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f4-dddt-9-3003: OPN deficiency impaired the induction of polarized Th1 responses to HBV antigens through DCs.Notes: T-cells were isolated from the WT and OPN−/− mice spleen by MACS and cocultured with CD11c+ cells isolated from the cell derived from murine BM of WT mice and OPN−/− mice after HBV antigenic stimulations at a ratio of 10:1, respectively, and then cytokines levels in the coculture supernatants were detected by ELISA. The levels of IFN-γ (A), TNF-α (B), IL-4 (C) and IL-10 (D) in the coculture supernatants are compared. *P<0.05; **P<0.01. ***P<0.001.Abbreviations: OPN, osteopontin; DCs, dendritic cells; HBV, hepatitis B virus; BM, bone marrow; WT, wild-type; MACS, magnetically activated cell sorting; HBcAg, hepatitis B core antigen; HBsAg, surface antigen of the hepatitis B virus; IL, interleukin; TNF, tumor necrosis factor; IFN, interferon; BMDC, bone marrow-derived dendritic cell; ELISA, enzyme-linked immunosorbent assay.

Mentions: We found that the levels of TNF-α and IFN-γ were significantly decreased while the levels of IL-4 and IL-10 were significantly elevated in the cocultured supernatants of OPN−/− DCs and WT T-cells compared with the cocultured supernatant of WT DCs and WT T-cells (Figure 4A–D). Similar results were observed in the cocultured supernatant of OPN−/− DCs and OPN−/− T-cells compared with the cocultured supernatant of WT DCs and OPN−/− T-cells (Figure 4A–D). Thus, these results show that the lack of OPN in DCs results in impaired induction of polarized Th1 responses and enhanced induction of polarized Th2 responses in the process of T-cell response induced by DCs after HBV antigenic stimulations. In addition, we found no significant difference in cytokines levels in the supernatant of WT DCs cocultured with WT T-cells or OPN−/− T-cells, and OPN−/− DCs co-cultured with WT T-cells or OPN−/− T-cells (Figure S1). These data show that the lack of OPN in T-cells was dispensable in regulatory effects of DCs on Th1/Th2 cytokines balance.


Osteopontin promotes dendritic cell maturation and function in response to HBV antigens.

Cui G, Chen J, He J, Lu C, Wei Y, Wang L, Xu X, Li L, Uede T, Diao H - Drug Des Devel Ther (2015)

OPN deficiency impaired the induction of polarized Th1 responses to HBV antigens through DCs.Notes: T-cells were isolated from the WT and OPN−/− mice spleen by MACS and cocultured with CD11c+ cells isolated from the cell derived from murine BM of WT mice and OPN−/− mice after HBV antigenic stimulations at a ratio of 10:1, respectively, and then cytokines levels in the coculture supernatants were detected by ELISA. The levels of IFN-γ (A), TNF-α (B), IL-4 (C) and IL-10 (D) in the coculture supernatants are compared. *P<0.05; **P<0.01. ***P<0.001.Abbreviations: OPN, osteopontin; DCs, dendritic cells; HBV, hepatitis B virus; BM, bone marrow; WT, wild-type; MACS, magnetically activated cell sorting; HBcAg, hepatitis B core antigen; HBsAg, surface antigen of the hepatitis B virus; IL, interleukin; TNF, tumor necrosis factor; IFN, interferon; BMDC, bone marrow-derived dendritic cell; ELISA, enzyme-linked immunosorbent assay.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4472071&req=5

f4-dddt-9-3003: OPN deficiency impaired the induction of polarized Th1 responses to HBV antigens through DCs.Notes: T-cells were isolated from the WT and OPN−/− mice spleen by MACS and cocultured with CD11c+ cells isolated from the cell derived from murine BM of WT mice and OPN−/− mice after HBV antigenic stimulations at a ratio of 10:1, respectively, and then cytokines levels in the coculture supernatants were detected by ELISA. The levels of IFN-γ (A), TNF-α (B), IL-4 (C) and IL-10 (D) in the coculture supernatants are compared. *P<0.05; **P<0.01. ***P<0.001.Abbreviations: OPN, osteopontin; DCs, dendritic cells; HBV, hepatitis B virus; BM, bone marrow; WT, wild-type; MACS, magnetically activated cell sorting; HBcAg, hepatitis B core antigen; HBsAg, surface antigen of the hepatitis B virus; IL, interleukin; TNF, tumor necrosis factor; IFN, interferon; BMDC, bone marrow-derived dendritic cell; ELISA, enzyme-linked immunosorbent assay.
Mentions: We found that the levels of TNF-α and IFN-γ were significantly decreased while the levels of IL-4 and IL-10 were significantly elevated in the cocultured supernatants of OPN−/− DCs and WT T-cells compared with the cocultured supernatant of WT DCs and WT T-cells (Figure 4A–D). Similar results were observed in the cocultured supernatant of OPN−/− DCs and OPN−/− T-cells compared with the cocultured supernatant of WT DCs and OPN−/− T-cells (Figure 4A–D). Thus, these results show that the lack of OPN in DCs results in impaired induction of polarized Th1 responses and enhanced induction of polarized Th2 responses in the process of T-cell response induced by DCs after HBV antigenic stimulations. In addition, we found no significant difference in cytokines levels in the supernatant of WT DCs cocultured with WT T-cells or OPN−/− T-cells, and OPN−/− DCs co-cultured with WT T-cells or OPN−/− T-cells (Figure S1). These data show that the lack of OPN in T-cells was dispensable in regulatory effects of DCs on Th1/Th2 cytokines balance.

Bottom Line: OPN secreted by DCs was compared.We found that OPN production of DCs from CHB patients was significantly lower than those from healthy volunteers.These findings suggested that OPN could improve the maturation and functioning of DCs in the immune response to HBV antigens, which might be useful to further improve the effect of DC vaccine.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China ; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, People's Republic of China.

ABSTRACT

Purpose: Dendritic cells (DCs) play critical roles in promoting innate and adaptive immunity in microbial infection. Functional impairment of DCs may mediate the suppression of viral-specific T-cell immune response in chronic hepatitis B (CHB) patients. Osteopontin (OPN) is involved in several liver diseases and infectious diseases. However, whether OPN affects DC function in hepatitis B virus (HBV) infection is unknown.

Methods: Twenty CHB patients and 20 healthy volunteers were recruited. OPN secreted by DCs was compared. Peripheral blood mononuclear cells cultured with OPN antibody were examined to study the costimulatory molecular expression and interleukin (IL)-12 production of DCs after HBV antigenic stimulation. OPN-deficient mice were used to investigate the influence of OPN on DC maturation and function after HBV antigenic stimulation in vitro and in vivo. Exogenous OPN was administrated to further verify the functioning of DCs from CHB patients upon HBV antigenic stimulation.

Results: We found that OPN production of DCs from CHB patients was significantly lower than those from healthy volunteers. The absence of OPN impaired IL-12 production and costimulatory molecular expression of DCs upon stimulation with HBV antigens. Defective DC function led to reduced activation of Th1 response to HBV antigens. In addition, OPN deficiency in DCs reduced the HBV antigen-induced inflammatory response in the liver of mice. Importantly, OPN administration significantly promoted the maturation of DCs from CHB patients in vitro.

Conclusion: These findings suggested that OPN could improve the maturation and functioning of DCs in the immune response to HBV antigens, which might be useful to further improve the effect of DC vaccine.

No MeSH data available.


Related in: MedlinePlus