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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 administration significantly promoted the maturation of DCs from CHB patients after HBcAg stimulation.Notes: The expressions of CD80 (A), CD86 (B), and HLA-DR (C) in BDCA-1+ cells from the peripheral blood of CHB patients following HBcAg stimulation with or without exogenous OPN administration were measured by flow cytometry. CHB patients, n=20. **P<0.01, ***P<0.001. (D) The percentages of IFN-γ-producing cell in CD3+ T-cells from the peripheral blood of CHB patients following HBcAg stimulation with or without exogenous OPN administration were measured by flow cytometry.Abbreviations: OPN, osteopontin; DCs, dendritic cells; CHB, chronic hepatitis B; HBV, hepatitis B virus; HBcAg, hepatitis B core antigen; IFN, interferon; HLA-DR, human leukocyte antigen-DR; BDCA-1, Blood Dendritic Cell Antigen 1.
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f6-dddt-9-3003: OPN administration significantly promoted the maturation of DCs from CHB patients after HBcAg stimulation.Notes: The expressions of CD80 (A), CD86 (B), and HLA-DR (C) in BDCA-1+ cells from the peripheral blood of CHB patients following HBcAg stimulation with or without exogenous OPN administration were measured by flow cytometry. CHB patients, n=20. **P<0.01, ***P<0.001. (D) The percentages of IFN-γ-producing cell in CD3+ T-cells from the peripheral blood of CHB patients following HBcAg stimulation with or without exogenous OPN administration were measured by flow cytometry.Abbreviations: OPN, osteopontin; DCs, dendritic cells; CHB, chronic hepatitis B; HBV, hepatitis B virus; HBcAg, hepatitis B core antigen; IFN, interferon; HLA-DR, human leukocyte antigen-DR; BDCA-1, Blood Dendritic Cell Antigen 1.

Mentions: Although several lines of evidences have demonstrated that the HBV-specific DC vaccine shows great promise for CHB patients,20–22 the generation of a more functional DC vaccine for the efficient therapy of CHB remains a challenge.22 Therefore, we tested whether exogenous OPN enhanced the function of DCs from CHB patients in vitro. Administration of exogenous OPN significantly increased the expression of CD80 and CD86 on BDCA-1+ cells from the peripheral blood of CHB patients following HBcAg stimulations (Figure 6A and B), while the expression of HLA-DR on BDCA-1+ cells showed no obvious difference after OPN addition (Figure 6C). Moreover, we further determined that the percentages of IFN-γ-producing T-cells were markedly increased after HBcAg stimulation combined with OPN compared to HBcAg stimulation alone (17.7% vs 4.5%, Figure 6D). These results suggested that OPN administration could significantly promote the functioning of DCs from CHB patients after HBV antigenic stimulation, which might have the potential to enhance the effect of HBV-specific DC vaccine.


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 administration significantly promoted the maturation of DCs from CHB patients after HBcAg stimulation.Notes: The expressions of CD80 (A), CD86 (B), and HLA-DR (C) in BDCA-1+ cells from the peripheral blood of CHB patients following HBcAg stimulation with or without exogenous OPN administration were measured by flow cytometry. CHB patients, n=20. **P<0.01, ***P<0.001. (D) The percentages of IFN-γ-producing cell in CD3+ T-cells from the peripheral blood of CHB patients following HBcAg stimulation with or without exogenous OPN administration were measured by flow cytometry.Abbreviations: OPN, osteopontin; DCs, dendritic cells; CHB, chronic hepatitis B; HBV, hepatitis B virus; HBcAg, hepatitis B core antigen; IFN, interferon; HLA-DR, human leukocyte antigen-DR; BDCA-1, Blood Dendritic Cell Antigen 1.
© Copyright Policy
Related In: Results  -  Collection

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

f6-dddt-9-3003: OPN administration significantly promoted the maturation of DCs from CHB patients after HBcAg stimulation.Notes: The expressions of CD80 (A), CD86 (B), and HLA-DR (C) in BDCA-1+ cells from the peripheral blood of CHB patients following HBcAg stimulation with or without exogenous OPN administration were measured by flow cytometry. CHB patients, n=20. **P<0.01, ***P<0.001. (D) The percentages of IFN-γ-producing cell in CD3+ T-cells from the peripheral blood of CHB patients following HBcAg stimulation with or without exogenous OPN administration were measured by flow cytometry.Abbreviations: OPN, osteopontin; DCs, dendritic cells; CHB, chronic hepatitis B; HBV, hepatitis B virus; HBcAg, hepatitis B core antigen; IFN, interferon; HLA-DR, human leukocyte antigen-DR; BDCA-1, Blood Dendritic Cell Antigen 1.
Mentions: Although several lines of evidences have demonstrated that the HBV-specific DC vaccine shows great promise for CHB patients,20–22 the generation of a more functional DC vaccine for the efficient therapy of CHB remains a challenge.22 Therefore, we tested whether exogenous OPN enhanced the function of DCs from CHB patients in vitro. Administration of exogenous OPN significantly increased the expression of CD80 and CD86 on BDCA-1+ cells from the peripheral blood of CHB patients following HBcAg stimulations (Figure 6A and B), while the expression of HLA-DR on BDCA-1+ cells showed no obvious difference after OPN addition (Figure 6C). Moreover, we further determined that the percentages of IFN-γ-producing T-cells were markedly increased after HBcAg stimulation combined with OPN compared to HBcAg stimulation alone (17.7% vs 4.5%, Figure 6D). These results suggested that OPN administration could significantly promote the functioning of DCs from CHB patients after HBV antigenic stimulation, which might have the potential to enhance the effect of HBV-specific DC vaccine.

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