CCL17 combined with CCL19 as a nasal adjuvant enhances the immunogenicity of an anti-caries DNA vaccine in rodents

Yan, Yan-hong; Yu, Fei; Cao, Li-Hua; Zhang, Zhou; Xu, Qingan

doi:10.1038/aps.2016.73

Cited by 13 publications

(7 citation statements)

References 34 publications

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“…Accumulating evidence indicates that, during immune response, antigen‐loaded dendritic cells enter the lymphatic vessels by releasing molecules that induce disruption of VE‐cadherin trans dimer‐mediated intercellular adhesion (“button”) between lymphatic lining cells. These molecules are groups of CRS motif‐containing growth factors (e.g., the PDGF superfamily) (Achen et al, ; Boensch et al,, ; Houck et al, ; Joukov et al, ; LaRochelle et al, ; Ostman et al, ; Pollock & Richardson, ;) and cytokines (e.g., IGFBP‐3, CCL1, CCL19, and CCL21) (Alvarez et al, ; Cao, ; Cao et al, ; Das et al, ; Huang et al, ; Johnson & Jackson, ; Lund et al, ; Roberti et al, ; Stacker et al, ; Yan et al, ) which bind to CRSBP‐1 (LYVE‐1) localized to the surface of lymphatic vessels. This stimulates a response, and acts like a token to gain entry to the lymphatic vessel network.…”

Section: Resultsmentioning

confidence: 99%

“…HA does not appear to affect PDGF‐BB binding to CRSBP‐1 (Huang et al, ). We hypothesize that high interstitial concentrations of HA may contribute to the phenotype of lymphedema by blocking the potential attenuating effects of endogenous growth factors/cytokines containing CRS motifs such as PDGF‐BB, VEGF‐A, IGFBP‐3, CCL1, CCL19, CCL21 (Alvarez et al, ; Das et al, ; Hou et al, ; Huang et al, , ; Johnson and Jackson, ; Lund et al, ; Roberti et al, ; Yan et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Both PDGF and VEGF peptides specifically interact with the AAAR domain of CRSBP‐1. In addition, PDGF‐BB, VEGF‐A, VEGF‐C, VEGF‐D, and other cytokines (e.g., FGF‐2, IGFBP‐3, CCL1, CCL19, and CCL21) containing CRS motifs have been shown to be involved in the transport of immune and cancer cells from the interstitial space into lymphatic vessel lumens (termed lymphatic entry) (Alvarez, Vollmann, & von Andrian, ; Cao, ; Cao et al, ; Das et al, ; Huang et al, ; Johnson & Jackson, ; Lund, Medler, Leachman, & Coussens, ; Roberti et al, ; Stacker et al, ; Yan et al, ). Since lymphatic entry of antigen‐presenting cells is known to be a rate‐limiting step in adaptive immunity (Teoh, Johnson, Hanke, McMichael, & Jackson, ), we hypothesize that CRSBP‐1, which controls lymphatic entry of cells, plays an important role in adaptive immunity.…”

Section: Introductionmentioning

confidence: 99%

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Development of the LYVE‐1 gene with an acidic‐amino‐acid‐rich (AAAR) domain in evolution is associated with acquisition of lymph nodes and efficient adaptive immunity

Huang

et al. 2017

Journal Cellular Physiology

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CRSBP-1 (mammalian LYVE-1) is a membrane glycoprotein highly expressed in lymphatic endothelial cells (LECs). It has multiple ligands, including hyaluronic acid (HA) and growth factors/cytokines (e.g., PDGF-BB and VEGF-A) containing CRS motifs (clusters of basic amino-acid residues). The ligand binding activities are mediated by Link module and acidic-amino-acid-rich (AAAR) domains, respectively. These CRSBP-1/LYVE-1 ligands have been shown to induce opening of lymphatic intercellular junctions in LEC monolayers and in lymphatic vessels in wild-type mice. We hypothesize that CRSBP-1/LYVE-1 ligands, particularly CRS-containing growth factors/cytokines, are secreted by immune and cancer cells for lymphatic entry during adaptive immune responses and lymphatic metastasis. We have looked into the origin of the Link module and AAAR domain of LYVE-1 in evolution and its association with the development of lymph nodes and efficient adaptive immunity. Lymph nodes represent the only major recent innovation of the adaptive immune systems in evolution particularly to mammals and bird. Here we demonstrate that the development of the LYVE-1 gene with the AAAR domain in evolution is associated with acquisition of lymph nodes and adaptive immunity. LYVE-1 from other species, which have no lymph nodes, lack the AAAR domain and efficient adaptive immunity. Synthetic CRSBP-1 ligands PDGF and VEGF peptides, which contain the CRS motifs of PDGF-BB and VEGF-A, respectively, specifically bind to CRSBP-1 but do not interact with either PDGFβR or VEGFR2. These peptides function as adjuvants by enhancing adaptive immunity of pseudorabies virus (PRV) vaccine in pigs. These results support the notion that LYVE-1 is involved in adaptive immunity in mammals.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development of the LYVE‐1 gene with an acidic‐amino‐acid‐rich (AAAR) domain in evolution is associated with acquisition of lymph nodes and efficient adaptive immunity

Huang

et al. 2017

Journal Cellular Physiology

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“…Nguyen-Hoai et al (2012) showed that recombinant plasmid encoding the human CCL19 gene and immunized mouse tumor models with the anti-tumor DNA vaccine pVax/E2A by gene gun, the results showed that CCL19 can enhance protection of vaccine and B cells function as APC. Yan et al (2016) pointed that a nasal adjuvant composed of CCL17 and CCL19 is used together with an anti-caries DNA vaccine, they can recruit more mature DC to secondary lymphoid tissues, induce the body to produce high titer antibodies, and reduce S mutants infection in rodents after vaccination. The results of T and B lymphocyte subsets percent, the expression diff erences of immune-related genes, and the RPS in p-CCL19-injected fi sh also showed that there was no signifi cant diff erence between the p-CCL19 group and the pBudCE4.1 group after immunization (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Two bicistronic DNA vaccines against Vibrio anguillarum and the immune effects on flounder Paralichthys olivaceus

Xing

Tang

et al. 2022

J. Ocean. Limnol.

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Chemokines are cytokines that can promote the activation and migration of immune cells, and increase the recognition of antigen by antigen-presenting cells (APC). Previous studies showed that a DNA vaccine can induce humoral and cellular immune responses of fl ounder after immunization. To explore the improvement of chemokines on the effi ciency of OmpK vaccine, two bicistronic DNA candidate vaccines were constructed and the immune responses they induced in the fl ounder were investigated by reverse transcription polymerase chain reaction (RT-PCR), indirect immunofl uorescent assay (IFA), H&E staining, fl ow cytometry (FCM), and quantifi cational real-time polymerase chain reaction (qRT-PCR). pBudCE4.1 plasmid as an expression vector, bicistronic DNA vaccines encoding OmpK gene and CC-motif ligand 4 gene (p-OmpK-CCL4), or Ompk gene and CC-motif ligand 19 gene (p-OmpK-CCL19) were successfully constructed. The results showed that two bicistronic DNA vaccines expressed Ompk protein of Vibrio anguillarum and CCL4/ CCL19 proteins of fl ounder both in vitro and in vivo. After immunization, a large number of leucocytes in muscle were recruited at the injection site in treatment groups. The constructed vaccines induced signifi cant increases in CD4-1 + and CD4-2 + T lymphocytes, and sIgM + B lymphocytes in peripheral blood, spleen, and head kidney. The percentage of T lymphocytes peaked on the 14 th post-vaccination day whereas that of B lymphocytes peaked in the 6 th post-vaccination week. Moreover, the expression profi les of 10 immune-related genes increased in muscles around the injection site, spleen, and head kidney. After the challenge, p-OmpK-CCL4 and p-OmpK-CCL19 conferred a relative percentage survival (RPS) of 74.1% and 63.3%, respectively, higher than p-OmpK alone (40.8%). In conclusion, both CCL4 and CCL19 can improve the protection of p-OmpK via evoking local immune response and then humoral and cellular immunity. CCL4 and CCL19 will be potential molecular adjuvants for use in DNA vaccines.

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“…To our knowledge, this is the first study to explore the effect of nicotine on the cariogenic potential of S. mutans in vivo . Regarding the sample sizes ranged from 6 to 10 rats for each group in most caries studies,29, 30, 31, 32, 33, 34 we took 16 rats and divided them into two groups (n = 8). The results of our study provide striking evidence that nicotine promotes the attachment of S. mutans to dental surface and the development of caries in vivo , and it appears to be a promotion factor for the development of dental caries.…”

Section: Discussionmentioning

confidence: 99%

Nicotine is a risk factor for dental caries: An in vivo study

Liu

Zhou

et al. 2018

Journal of Dental Sciences

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Background/purpose Streptococcus mutans is an important pathogen in the development of dental caries. Many studies have focused on the relationship between nicotine and S. mutans in vitro . The aim of this study was to investigate the effect of nicotine on the growth of S. mutans and its cariogenic potential in vivo . Materials and methods Sixteen male Specific-pathogen-free Wistar rats were divided into 2 groups (nicotine-treated and nicotine-untreated group) and infected with S. mutans . The S. mutans suspension was treated with 1 mg/mL nicotine in the nicotine-treated group. The Keyes method was used to evaluate sulcal caries of rats, and dental plaque on molar teeth was observed by scanning electron microscopy (SEM). Results Incidence of sulcal caries was higher in nicotine-treated group compared to nicotine-untreated group (42.7 ± 1.7 vs 37.3 ± 4.9, P = 0.009). Severity of caries increased with nicotine treatment. The slightly dentinal caries scores and moderate dentinal caries scores were higher in the presence of nicotine (P < 0.001). Increased number of S. mutans cells attached to dental surface was observed under SEM in the nicotine-treated group. Conclusion Nicotine would promote the attachment of S. mutans to dental surface, and further increase the incidence and severity of dental caries. Therefore, nicotine might be a risk factor for smoking-induced caries.

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CCL17 combined with CCL19 as a nasal adjuvant enhances the immunogenicity of an anti-caries DNA vaccine in rodents

Abstract: A nasal adjuvant consisting of a combination of CCL17 and CCL19 attracts more mature DCs to secondary lymphoid tissues, inducing enhanced antibody responses against the anti-caries DNA vaccine pCIA-P and reducing S mutans infection in rodents.

Cited by 13 publications

References 34 publications

Development of the LYVE‐1 gene with an acidic‐amino‐acid‐rich (AAAR) domain in evolution is associated with acquisition of lymph nodes and efficient adaptive immunity

Development of the LYVE‐1 gene with an acidic‐amino‐acid‐rich (AAAR) domain in evolution is associated with acquisition of lymph nodes and efficient adaptive immunity

Two bicistronic DNA vaccines against Vibrio anguillarum and the immune effects on flounder Paralichthys olivaceus

Nicotine is a risk factor for dental caries: An in vivo study

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