Limits...
Dendritic Cells Regulate Treg-Th17 Axis in Obstructive Phase of Bile Duct Injury in Murine Biliary Atresia.

Liu YJ, Li K, Yang L, Tang ST, Wang XX, Cao GQ, Li S, Lei HY, Zhang X - PLoS ONE (2015)

Bottom Line: By depleting the Th17 cells, the BA symptoms (onset of jaundice, acholic stools and retarded growth) were attenuated and the survival rate was improved.The level of IL-6, which has been shown to be abundantly secreted by activated dendritic cells (DCs), was remarkably elevated.In conclusion, the DC-regulated Treg-Th17 axis, probably in conjunction with other effector T cells, aggravates progressive inflammatory injury at the time of ductal obstruction.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

ABSTRACT
Several cell types are considered to be effector cells in bile duct injury in rhesus rotavirus (RRV)-induced experimental biliary atresia (BA). Here, we identified an increased T helper 17 (Th17) cell population in a BA mode. By depleting the Th17 cells, the BA symptoms (onset of jaundice, acholic stools and retarded growth) were attenuated and the survival rate was improved. Furthermore, we found that in mice with BA, the percentage of CD4+CD25highFoxp3+ T regulatory (Treg) cells decreased along with the increased percentage of Th17 cells. However, the absolute numbers of Treg and Th17 cells were both increased in liver of RRV-injected mice compared to saline-injected mice. The proportion of Th17 cells at 7 days post-infection was decreased if Treg cells isolated from normal adult mice, but not Treg cells from the livers of mice with BA, were intraperitoneally transferred on day 5 of life. In vitro experiments also showed that Treg cells from mice with BA had a diminished suppressive effect on Th17 cell generation. To determine the mechanisms, we investigated the production of cytokines in the liver. The level of IL-6, which has been shown to be abundantly secreted by activated dendritic cells (DCs), was remarkably elevated. Importantly, in a Treg/Th17 cell suppression assay, IL-6 was demonstrated to paralyze the Treg cells' suppressive effect on Th17 cells and eventually the unrestrained increase of Th17 cells contributed to bile duct injury. In conclusion, the DC-regulated Treg-Th17 axis, probably in conjunction with other effector T cells, aggravates progressive inflammatory injury at the time of ductal obstruction.

No MeSH data available.


Related in: MedlinePlus

The proportion of Treg decreases and the proportion of Th17 cells increases, but the absolute numbers of both are increased.(A and B) At the time of bile ductal obstruction, flow cytometry analysis showed that the percentage of Tregs decreased but Th17 increased in the liver of the RRV group compared to the saline group. The percentage of CD4+ cells positive for the indicated marker is shown. P = 0.0245 for the Treg group and P<0.001 for the Th17 group, n = 11 for each group. (C) Absolute numbers of Tregs increased 2.6 fold and Th17 increased 34 fold in the RRV challenged group compared to the saline control group. Numbers were measured per individual liver by FCM, * P<0.05, ** P<0.01, n = 5 for each group.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4556529&req=5

pone.0136214.g003: The proportion of Treg decreases and the proportion of Th17 cells increases, but the absolute numbers of both are increased.(A and B) At the time of bile ductal obstruction, flow cytometry analysis showed that the percentage of Tregs decreased but Th17 increased in the liver of the RRV group compared to the saline group. The percentage of CD4+ cells positive for the indicated marker is shown. P = 0.0245 for the Treg group and P<0.001 for the Th17 group, n = 11 for each group. (C) Absolute numbers of Tregs increased 2.6 fold and Th17 increased 34 fold in the RRV challenged group compared to the saline control group. Numbers were measured per individual liver by FCM, * P<0.05, ** P<0.01, n = 5 for each group.

Mentions: In the present study, Treg cells were defined by expression of the surface markers CD4 and CD25 and the transcription factor Foxp3 (CD4+CD25highFoxp3+). The majority of this subset was CD127- (96–98%, data not shown). We found that the Treg cell proportion decreased in livers at the 7th day post-RRV injection compared with the proportion in saline-injected mice (4.19 ± 1.62% vs 2.75 ± 1.11%, P = 0.025, n = 11, Fig 3A). In contrast, the percentage of Th17 cells increased 8.0-fold (0.48 ± 0.34% vs 3.83 ± 1.31%, n = 11, P<0.000, Fig 3B). However, the absolute numbers of Treg cells and Th17 cells increased 2.6-fold (3,477 ± 793/liver in the saline group vs 9,075 ± 1,998/liver in the RRV group, P = 0.011) and 34-fold (365 ± 133/liver in the saline group vs 12,410 ± 2,887/liver in the RRV group, P = 0.002), respectively (Fig 3C).


Dendritic Cells Regulate Treg-Th17 Axis in Obstructive Phase of Bile Duct Injury in Murine Biliary Atresia.

Liu YJ, Li K, Yang L, Tang ST, Wang XX, Cao GQ, Li S, Lei HY, Zhang X - PLoS ONE (2015)

The proportion of Treg decreases and the proportion of Th17 cells increases, but the absolute numbers of both are increased.(A and B) At the time of bile ductal obstruction, flow cytometry analysis showed that the percentage of Tregs decreased but Th17 increased in the liver of the RRV group compared to the saline group. The percentage of CD4+ cells positive for the indicated marker is shown. P = 0.0245 for the Treg group and P<0.001 for the Th17 group, n = 11 for each group. (C) Absolute numbers of Tregs increased 2.6 fold and Th17 increased 34 fold in the RRV challenged group compared to the saline control group. Numbers were measured per individual liver by FCM, * P<0.05, ** P<0.01, n = 5 for each group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556529&req=5

pone.0136214.g003: The proportion of Treg decreases and the proportion of Th17 cells increases, but the absolute numbers of both are increased.(A and B) At the time of bile ductal obstruction, flow cytometry analysis showed that the percentage of Tregs decreased but Th17 increased in the liver of the RRV group compared to the saline group. The percentage of CD4+ cells positive for the indicated marker is shown. P = 0.0245 for the Treg group and P<0.001 for the Th17 group, n = 11 for each group. (C) Absolute numbers of Tregs increased 2.6 fold and Th17 increased 34 fold in the RRV challenged group compared to the saline control group. Numbers were measured per individual liver by FCM, * P<0.05, ** P<0.01, n = 5 for each group.
Mentions: In the present study, Treg cells were defined by expression of the surface markers CD4 and CD25 and the transcription factor Foxp3 (CD4+CD25highFoxp3+). The majority of this subset was CD127- (96–98%, data not shown). We found that the Treg cell proportion decreased in livers at the 7th day post-RRV injection compared with the proportion in saline-injected mice (4.19 ± 1.62% vs 2.75 ± 1.11%, P = 0.025, n = 11, Fig 3A). In contrast, the percentage of Th17 cells increased 8.0-fold (0.48 ± 0.34% vs 3.83 ± 1.31%, n = 11, P<0.000, Fig 3B). However, the absolute numbers of Treg cells and Th17 cells increased 2.6-fold (3,477 ± 793/liver in the saline group vs 9,075 ± 1,998/liver in the RRV group, P = 0.011) and 34-fold (365 ± 133/liver in the saline group vs 12,410 ± 2,887/liver in the RRV group, P = 0.002), respectively (Fig 3C).

Bottom Line: By depleting the Th17 cells, the BA symptoms (onset of jaundice, acholic stools and retarded growth) were attenuated and the survival rate was improved.The level of IL-6, which has been shown to be abundantly secreted by activated dendritic cells (DCs), was remarkably elevated.In conclusion, the DC-regulated Treg-Th17 axis, probably in conjunction with other effector T cells, aggravates progressive inflammatory injury at the time of ductal obstruction.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

ABSTRACT
Several cell types are considered to be effector cells in bile duct injury in rhesus rotavirus (RRV)-induced experimental biliary atresia (BA). Here, we identified an increased T helper 17 (Th17) cell population in a BA mode. By depleting the Th17 cells, the BA symptoms (onset of jaundice, acholic stools and retarded growth) were attenuated and the survival rate was improved. Furthermore, we found that in mice with BA, the percentage of CD4+CD25highFoxp3+ T regulatory (Treg) cells decreased along with the increased percentage of Th17 cells. However, the absolute numbers of Treg and Th17 cells were both increased in liver of RRV-injected mice compared to saline-injected mice. The proportion of Th17 cells at 7 days post-infection was decreased if Treg cells isolated from normal adult mice, but not Treg cells from the livers of mice with BA, were intraperitoneally transferred on day 5 of life. In vitro experiments also showed that Treg cells from mice with BA had a diminished suppressive effect on Th17 cell generation. To determine the mechanisms, we investigated the production of cytokines in the liver. The level of IL-6, which has been shown to be abundantly secreted by activated dendritic cells (DCs), was remarkably elevated. Importantly, in a Treg/Th17 cell suppression assay, IL-6 was demonstrated to paralyze the Treg cells' suppressive effect on Th17 cells and eventually the unrestrained increase of Th17 cells contributed to bile duct injury. In conclusion, the DC-regulated Treg-Th17 axis, probably in conjunction with other effector T cells, aggravates progressive inflammatory injury at the time of ductal obstruction.

No MeSH data available.


Related in: MedlinePlus