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Activated IL-23/IL-17 pathway closely correlates with increased Foxp3 expression in livers of chronic hepatitis B patients.

Wang Q, Zheng Y, Huang Z, Tian Y, Zhou J, Mao Q, Wu Y, Ni B - BMC Immunol. (2011)

Bottom Line: The intrahepatic expression of Foxp3 strongly correlated with the copies of HBV DNA and the concentration of surface antigen, HBsAg.IL-23/IL-17 pathway-related proinflammatory cytokines were also found to be significantly increased in patients' liver tissues, as compared to healthy controls.Moreover, Foxp3 expression was strikingly correlated with the production of these cytokines in liver tissues of CHB patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.

ABSTRACT

Background: Foxp3 protein plays a critical role in mediating the inflammatory response and can inhibit the proinflammatory IL-23/IL-17 pathway. However, the molecular interplay of Foxp3 and the IL-23/IL-17 pathway in patients with chronic hepatitis B (CHB) remains unclear. To this end, we analyzed the expression patterns of Foxp3- and IL-23/IL-17 pathway-related proinflammatory cytokines in 39 patients with acute-on-chronic liver failure, 71 patients with CHB and 32 healthy controls.

Results: Foxp3 expression was found to be elevated in and mainly expressed by the CD4+ T cell sub-population of peripheral blood mononuclear cells and liver tissues of patients with hepatitis B. The intrahepatic expression of Foxp3 strongly correlated with the copies of HBV DNA and the concentration of surface antigen, HBsAg. IL-23/IL-17 pathway-related proinflammatory cytokines were also found to be significantly increased in patients' liver tissues, as compared to healthy controls. Moreover, Foxp3 expression was strikingly correlated with the production of these cytokines in liver tissues of CHB patients.

Conclusions: The closely-correlated increase of Foxp3 and IL-23/IL-17 pathway activity in HBV-infected livers suggests that the proinflammatory IL-23/IL-17 pathway had not been effectively suppressed by the host immune machinery, such as Treg (Foxp3) cells. Constitutive activation of the IL-23/17 pathway, thus, may support the chronic hepatitis B state.

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Foxp3 expression is significantly higher in peripheral blood of patients with CHB. PBMC from healthy controls and patients with CHB or ACLF were used to detect the expression levels of Foxp3 by qPCR (A) and flow cytometry (B and C). (A) Relative mRNA expression of Foxp3 in PBMC. (B) Pooled data indicating the percentages of Foxp3+ cells in total CD4+ T cells. (C) Representative dotplots of Foxp3+ cells in CD4+ T cells. The values in the quadrants indicate the percentage of each CD4+ T cell subset. Error bars indicate SD; *, P < 0.05; **, P < 0.01; ***, P < 0.001.
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Figure 1: Foxp3 expression is significantly higher in peripheral blood of patients with CHB. PBMC from healthy controls and patients with CHB or ACLF were used to detect the expression levels of Foxp3 by qPCR (A) and flow cytometry (B and C). (A) Relative mRNA expression of Foxp3 in PBMC. (B) Pooled data indicating the percentages of Foxp3+ cells in total CD4+ T cells. (C) Representative dotplots of Foxp3+ cells in CD4+ T cells. The values in the quadrants indicate the percentage of each CD4+ T cell subset. Error bars indicate SD; *, P < 0.05; **, P < 0.01; ***, P < 0.001.

Mentions: Tregs with transcription factor Foxp3 play an pivotal role in controlling immune response mediated inflammation [16]. Several reports have shown evidence that Treg cells are involved in hepatitis B pathogenesis [6-10]. To further explore the role of Foxp3 in patients with hepatitis B, we collected the peripheral blood from 34 CHB patients and 30 ACLF patients, and then evaluated the expression of Foxp3 as detected by qPCR and FCM assays. As shown in Figure 1A, the expression of Foxp3 mRNA was found to be significantly increased in PBMC of CHB and ACLF patients, as compared with healthy controls. FCM assays indicated that the Foxp3+ T cell portion of CD4+ T cells were markedly up-regulated in HBV-infected patients; the ACLF patients had the most Foxp3+ T cells (Figure 1B and 1C).


Activated IL-23/IL-17 pathway closely correlates with increased Foxp3 expression in livers of chronic hepatitis B patients.

Wang Q, Zheng Y, Huang Z, Tian Y, Zhou J, Mao Q, Wu Y, Ni B - BMC Immunol. (2011)

Foxp3 expression is significantly higher in peripheral blood of patients with CHB. PBMC from healthy controls and patients with CHB or ACLF were used to detect the expression levels of Foxp3 by qPCR (A) and flow cytometry (B and C). (A) Relative mRNA expression of Foxp3 in PBMC. (B) Pooled data indicating the percentages of Foxp3+ cells in total CD4+ T cells. (C) Representative dotplots of Foxp3+ cells in CD4+ T cells. The values in the quadrants indicate the percentage of each CD4+ T cell subset. Error bars indicate SD; *, P < 0.05; **, P < 0.01; ***, P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3094328&req=5

Figure 1: Foxp3 expression is significantly higher in peripheral blood of patients with CHB. PBMC from healthy controls and patients with CHB or ACLF were used to detect the expression levels of Foxp3 by qPCR (A) and flow cytometry (B and C). (A) Relative mRNA expression of Foxp3 in PBMC. (B) Pooled data indicating the percentages of Foxp3+ cells in total CD4+ T cells. (C) Representative dotplots of Foxp3+ cells in CD4+ T cells. The values in the quadrants indicate the percentage of each CD4+ T cell subset. Error bars indicate SD; *, P < 0.05; **, P < 0.01; ***, P < 0.001.
Mentions: Tregs with transcription factor Foxp3 play an pivotal role in controlling immune response mediated inflammation [16]. Several reports have shown evidence that Treg cells are involved in hepatitis B pathogenesis [6-10]. To further explore the role of Foxp3 in patients with hepatitis B, we collected the peripheral blood from 34 CHB patients and 30 ACLF patients, and then evaluated the expression of Foxp3 as detected by qPCR and FCM assays. As shown in Figure 1A, the expression of Foxp3 mRNA was found to be significantly increased in PBMC of CHB and ACLF patients, as compared with healthy controls. FCM assays indicated that the Foxp3+ T cell portion of CD4+ T cells were markedly up-regulated in HBV-infected patients; the ACLF patients had the most Foxp3+ T cells (Figure 1B and 1C).

Bottom Line: The intrahepatic expression of Foxp3 strongly correlated with the copies of HBV DNA and the concentration of surface antigen, HBsAg.IL-23/IL-17 pathway-related proinflammatory cytokines were also found to be significantly increased in patients' liver tissues, as compared to healthy controls.Moreover, Foxp3 expression was strikingly correlated with the production of these cytokines in liver tissues of CHB patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.

ABSTRACT

Background: Foxp3 protein plays a critical role in mediating the inflammatory response and can inhibit the proinflammatory IL-23/IL-17 pathway. However, the molecular interplay of Foxp3 and the IL-23/IL-17 pathway in patients with chronic hepatitis B (CHB) remains unclear. To this end, we analyzed the expression patterns of Foxp3- and IL-23/IL-17 pathway-related proinflammatory cytokines in 39 patients with acute-on-chronic liver failure, 71 patients with CHB and 32 healthy controls.

Results: Foxp3 expression was found to be elevated in and mainly expressed by the CD4+ T cell sub-population of peripheral blood mononuclear cells and liver tissues of patients with hepatitis B. The intrahepatic expression of Foxp3 strongly correlated with the copies of HBV DNA and the concentration of surface antigen, HBsAg. IL-23/IL-17 pathway-related proinflammatory cytokines were also found to be significantly increased in patients' liver tissues, as compared to healthy controls. Moreover, Foxp3 expression was strikingly correlated with the production of these cytokines in liver tissues of CHB patients.

Conclusions: The closely-correlated increase of Foxp3 and IL-23/IL-17 pathway activity in HBV-infected livers suggests that the proinflammatory IL-23/IL-17 pathway had not been effectively suppressed by the host immune machinery, such as Treg (Foxp3) cells. Constitutive activation of the IL-23/17 pathway, thus, may support the chronic hepatitis B state.

Show MeSH
Related in: MedlinePlus