Imbalances of CD4+ T-cell subgroups in Crohn's disease and their relationship with disease activity and prognosis

被引:50
作者
Chao, Kang [1 ]
Zhang, Shenghong [1 ]
Yao, Jiayan [1 ]
He, Yao [1 ]
Chen, Baili [1 ]
Zeng, Zhirong [1 ]
Zhong, Bihui [1 ]
Chen, Minhu [1 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 1, Div Gastroenterol, Guangzhou 510080, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Crohn's disease; recurrence; Th cell; transcription factors; Treg cell; INFLAMMATORY-BOWEL-DISEASE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TH17; CELLS; ULCERATIVE-COLITIS; IFN-GAMMA; EXPRESSION; INDUCTION; PATHOGENESIS; THERAPY;
D O I
10.1111/jgh.12592
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background and AimThe CD4(+) T-cell subgroups play central pathophysiological roles in Crohn's disease (CD); however, their clinical relevance requires additional clarification and remains controversial. We investigated their balance in Chinese CD patients and explored their clinical significance. MethodsPeripheral blood mononuclear cells and serum were collected from 46 Chinese CD patients and 23 healthy donors. Circulating Treg, Th1, Th2, and Th17 cells were flow cytometrically analyzed. Subgroup-restricted transcription factor expression was determined by real-time polymerase chain reaction. Serum concentrations of the main cytokines produced by each subgroup were measured by cytometric bead arrays or enzyme-linked immunosorbent assay. ResultsLower Treg proportion (6.01.2% vs 7.8 +/- 1.5%, P=0.030), FOXP3 mRNA expression (0.58-fold, P=0.030), and circulating soluble TGF-1 (19.1 +/- 9.9 vs 32.7 +/- 16.8ng/mL, P=0.038) were observed in CD patients versus controls. The Th1 and Th17 proportions were higher in CD patients (17.8 +/- 6.6% vs 7.8 +/- 1.5%, P<0.001; and 3.7 +/- 1.8% vs 1.8 +/- 0.7%, P=0.022, respectively), as were transcription factors T-bet (4.6-fold, P=0.043) and RORt (14-fold, P<0.001) and related cytokines (P<0.05). Th2 proportion, GATA3 mRNA expression, and serum interleukin-4 concentration in CD patients were similar to controls (P>0.05). Treg/Th1 and Treg/Th17 ratios were higher in inactive versus active CD patients (0.6 +/- 0.4 vs 0.3 +/- 0.1, P=0.022; and 3.7 +/- 2.0 vs 1.7 +/- 1.4, P=0.013, respectively). During follow-up, patients with lower Treg/Th1 and Treg/Th17 ratios were at higher recurrence risk. ConclusionsImbalances among Treg, Th1, and Th17 subgroups were found in Chinese CD patients. Treg/Th1 and Treg/Th17 ratios are associated with disease activity and are potential prognostic indicators for predicting CD recurrence.
引用
收藏
页码:1808 / 1814
页数:7
相关论文
共 29 条
[1]   More stories on Th17 cells [J].
Basso, Alexandre S. ;
Cheroutre, Hilde ;
Mucida, Daniel .
CELL RESEARCH, 2009, 19 (04) :399-411
[2]   Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease [J].
Brand, S. .
GUT, 2009, 58 (08) :1152-1167
[3]   Altered expression of inteferon-γ and interleukin-4 in inflammatory bowel disease [J].
Camoglio, L ;
Velde, AAT ;
Tigges, TJ ;
Das, PK ;
Van Deventer, SJH .
INFLAMMATORY BOWEL DISEASES, 1998, 4 (04) :285-290
[4]   Reduction of CD68+ Macrophages and Decreased IL-17 Expression in Intestinal Mucosa of Patients with Inflammatory Bowel Disease Strongly Correlate With Endoscopic Response and Mucosal Healing following Infliximab Therapy [J].
Caprioli, Flavio ;
Bose, Francesca ;
Rossi, Riccardo L. ;
Petti, Luciana ;
Vigano, Chiara ;
Ciafardini, Clorinda ;
Raeli, Lorenzo ;
Basilisco, Guido ;
Ferrero, Stefano ;
Pagani, Massimiliano ;
Conte, Dario ;
Altomare, Gianfranco ;
Monteleone, Giovanni ;
Abrignani, Sergio ;
Reali, Eva .
INFLAMMATORY BOWEL DISEASES, 2013, 19 (04) :729-739
[5]   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
[6]  
Fuss IJ, 1996, J IMMUNOL, V157, P1261
[7]   The role of T-regulatory cells and Toll-like receptors in the pathogenesis of human inflammatory bowel disease [J].
Himmel, Megan E. ;
Hardenberg, Gijs ;
Piccirillo, Ciriaco A. ;
Steiner, Theodore S. ;
Levings, Megan K. .
IMMUNOLOGY, 2008, 125 (02) :145-153
[8]   Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis [J].
Hofstetter, HH ;
Ibrahim, SM ;
Koczan, D ;
Kruse, N ;
Weishaupt, A ;
Toyka, KV ;
Gold, R .
CELLULAR IMMUNOLOGY, 2005, 237 (02) :123-130
[9]   Characterization of Interleukin-17-Producing Regulatory T Cells in Inflamed Intestinal Mucosa From Patients With Inflammatory Bowel Diseases [J].
Hovhannisyan, Zaruhi ;
Treatman, Jacquelyn ;
Littman, Dan R. ;
Mayer, Lloyd .
GASTROENTEROLOGY, 2011, 140 (03) :957-965
[10]   Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial [J].
Hueber, Wolfgang ;
Sands, Bruce E. ;
Lewitzky, Steve ;
Vandemeulebroecke, Marc ;
Reinisch, Walter ;
Higgins, Peter D. R. ;
Wehkamp, Jan ;
Feagan, Brian G. ;
Yao, Michael D. ;
Karczewski, Marek ;
Karczewski, Jacek ;
Pezous, Nicole ;
Bek, Stephan ;
Bruin, Gerard ;
Mellgard, Bjoern ;
Berger, Claudia ;
Londei, Marco ;
Bertolino, Arthur P. ;
Tougas, Gervais ;
Travis, Simon P. L. .
GUT, 2012, 61 (12) :1693-1700