Elevated Th17 cells accompanied by decreased regulatory T cells and cytokine environment in infants with biliary atresia

被引：41
作者：
Yang, Ying [1 ]
Liu, Yong-jun [1 ]
Tang, Shao-tao [1 ]
Yang, Li [1 ]
Yang, Jun [1 ]
Cao, Guo-qing [1 ]
Zhang, Jing-hui [1 ]
Wang, Xin-xin [1 ]
Mao, Yong-zhong [1 ]
机构：
[1] Huazhong Univ Sci & Technol, Union Hosp, Dept Pediat Surg, Tongji Med Coll, Wuhan 430022, Peoples R China
来源：
PEDIATRIC SURGERY INTERNATIONAL | 2013年 / 29卷 / 12期
基金：
中国国家自然科学基金;
关键词：
Biliary atresia; Th17; cells; T-reg cells; GROWTH-FACTOR-BETA; EFFECTOR-CELLS; INDUCED FOXP3; TGF-BETA; DIFFERENTIATION; INTERLEUKIN-17; T(H)17; CD4(+); ACTIVATION; EXPRESSION;
D O I：
10.1007/s00383-013-3421-6
中图分类号：
R72 [儿科学];
学科分类号：
100202 ;
摘要：
The aim of this study was to investigate the role of Th17 and T-reg cells in biliary atresia (BA) and to assess the liver cytokine environment in BA patients. The percentages of Th17 and T-reg cells in peripheral blood mononuclear cells (PBMCs) of BA patients and healthy controls (HC) were evaluated. The serum concentrations of IL-17a and IL-23 as well as Foxp3, IL-17a, ROR-gamma t, IL-6, IL-1 beta and TGF-beta 1 m-RNA and protein expressions in liver tissues and the number of Foxp3, IL-17a, ROR-gamma t, CD4 expressing cells which infiltrated the hepatic tissues were determined. The Th17/T-reg cell ratio (P < 0.001) and blood concentrations of IL-17a and IL-23 (P < 0.05) were increased in the BA as compared to the HC group. Expressions of Foxp3, ROR-gamma t, IL-17a, IL-1 beta, IL-6 as well as TGF-beta 1 mRNA and proteins were significantly increased in BA as compared to HC livers (P < 0.01, P < 0.05). High levels of IL-17a/ROR-gamma t-positive and moderate levels of Foxp3-positive cells infiltrated damaged BA bile ducts and the ratio of FoxP3(+) T to CD4(+) T cells was significantly lower in BA than in HC samples (P < 0.01). Cytokine-induced imbalance between Th17 and T-reg cells in BA livers may be involved in bile duct damage.
引用
收藏
页码：1249 / 1260
页数：12
相关论文
共 40 条
[1]   Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells [J].
Acosta-Rodriguez, Eva V. ;
Napolitani, Giorgio ;
Lanzavecchia, Antonio ;
Sallusto, Federica .
NATURE IMMUNOLOGY, 2007, 8 (09) :942-949
[2]   Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production [J].
Allan, Sarah E. ;
Crome, Sarah Q. ;
Crellin, Natasha K. ;
Passerini, Laura ;
Steiner, Theodore S. ;
Bacchetta, Rosa ;
Roncarolo, Maria G. ;
Levings, Megan K. .
INTERNATIONAL IMMUNOLOGY, 2007, 19 (04) :345-354
[3]   IL-17-producing human peripheral regulatory T cells retain suppressive function [J].
Beriou, Gaelle ;
Costantino, Cristina M. ;
Ashley, Charles W. ;
Yang, Li ;
Kuchroo, Vijay K. ;
Baecher-Allan, Clare ;
Hafler, David A. .
BLOOD, 2009, 113 (18) :4240-4249
[4]   Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J].
Bettelli, E ;
Carrier, YJ ;
Gao, WD ;
Korn, T ;
Strom, TB ;
Oukka, M ;
Weiner, HL ;
Kuchroo, VK .
NATURE, 2006, 441 (7090) :235-238
[5]   Genetic induction of proinflammatory immunity in children with billary atresia [J].
Bezerra, JA ;
Tiao, G ;
Ryckman, FC ;
Alonso, M ;
Sabla, GE ;
Shneider, B ;
Sokol, RJ ;
Aronow, BJ .
LANCET, 2002, 360 (9346) :1653-1659
[6]   Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells [J].
Brindley, Stephen M. ;
Lanham, Allison M. ;
Karrer, Frederick M. ;
Tucker, Rebecca M. ;
Fontenot, Andrew P. ;
Mack, Cara L. .
HEPATOLOGY, 2012, 55 (04) :1130-1138
[7]   Foxp3+ Regulatory T Cells, Th17 Effector Cells, and Cytokine Environment in Inflammatory Bowel Disease [J].
Eastaff-Leung, Nicola ;
Mabarrack, Nicholas ;
Barbour, Angela ;
Cummins, Adrian ;
Barry, Simon .
JOURNAL OF CLINICAL IMMUNOLOGY, 2010, 30 (01) :80-89
[8]   An overview of IL-17 function and signaling [J].
Gaffen, Sarah L. .
CYTOKINE, 2008, 43 (03) :402-407
[9]   Diagnostic value of hepatic intercellular adhesion molecule-1 expression in Egyptian infants with biliary atresia and other forms of neonatal cholestasis [J].
Ghoneim, Enas M. ;
Sira, Mostafa M. ;
Elaziz, Azza M. Abd ;
Khalil, Fatma O. ;
Sultan, Mervat M. ;
Mahmoud, Ahmed B. .
HEPATOLOGY RESEARCH, 2011, 41 (08) :763-775
[10]   Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages [J].
Harrington, LE ;
Hatton, RD ;
Mangan, PR ;
Turner, H ;
Murphy, TL ;
Murphy, KM ;
Weaver, CT .
NATURE IMMUNOLOGY, 2005, 6 (11) :1123-1132
1234