Mucosal Immunity Related to FOXP3+ Regulatory T Cells, Th17 Cells and Cytokines in Pediatric Inflammatory Bowel Disease

被引:35
作者
Cho, Jinhee [1 ]
Kim, Sorina [2 ]
Yang, Da Hee [2 ]
Lee, Juyeon [2 ]
Park, Kyeong Won [2 ]
Go, Junyong [2 ]
Hyun, Chang-Lim [3 ]
Jee, Youngheun [1 ]
Kang, Ki Soo [2 ,4 ]
机构
[1] Jeju Natl Univ, Dept Vet Med, 102 Jejudaehak Ro, Jeju 63243, South Korea
[2] Jeju Natl Univ Hosp, Dept Pediat, Jeju, South Korea
[3] Jeju Natl Univ, Sch Med, Dept Pathol, Jeju, South Korea
[4] Jeju Natl Univ, Sch Med, Dept Pediat, Jeju, South Korea
关键词
Inflammatory Bowel Disease; FOXP3(+ ); Th17; Cytokine; CROHNS-DISEASE; PLASTICITY; EFFICACY; THERAPY; SAFETY; IBD;
D O I
10.3346/jkms.2018.33.e336
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: We aimed to investigate mucosal immunity related to forkhead box P3 (FOXP3(+)) regulatory T (Treg) cells, T helper 17 (Th17) cells and cytokines in pediatric inflammatory bowel disease (IBD). Methods: Mucosal tissues from terminal ileum and colon and serum samples were collected from twelve children with IBD and seven control children. Immunohistochemical staining was done using anti-human FOXP3 and anti-ROR gamma t antibodies. Serum levels of cytokines were analyzed using a multiplex assay covering interleukin (IL)-1 beta, IL-4, IL-6, IL 10, IL-17A/F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon (IFN)-gamma, soluble CD40L, and tumor necrosis factor-alpha. Results: FOXP3(+) Treg cells in the lamina propria (LP) of terminal ileum of patients with Crohn's disease were significantly (P < 0.05) higher than those in the healthy controls. ROR gamma t(+) T cells of terminal ileum tended to be higher in Crohn's disease than those in the control. In the multiplex assay, serum concentrations (pg/mL) of IL-4 (9.6 +/- 1.5 vs. 12.7 +/- 3.0), IL-21 (14.9 +/- 1.5 vs. 26.4 +/- 9.1), IL-33 (14.3 +/- 0.9 vs. 19.1 +/- 5.3), and IFN-gamma (15.2 +/- 5.9 vs. 50.2 +/- 42.4) were significantly lower in Crohn's disease than those in the control group. However, serum concentration of IL-6 (119.1 +/- 79.6 vs. 52.9 +/- 39.1) was higher in Crohn's disease than that in the control. Serum concentrations of IL-17A (64.2 +/- 17.2 vs. 28.3 +/- 10.0) and IL-22 (37.5 +/- 8.8 vs. 27.2 +/- 3.7) were significantly higher in ulcerative colitis than those in Crohn's disease. Conclusion: Mucosal immunity analysis showed increased FOXP3(+) T reg cells in the LP with Crohn's disease while Th17 cell polarizing and signature cytokines were decreased in the serum samples of Crohn's disease but increased in ulcerative colitis.
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页数:12
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共 31 条
[1]   MECHANISMS OF DISEASE Inflammatory Bowel Disease [J].
Abraham, Clara ;
Cho, Judy H. .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (21) :2066-2078
[2]   Increased number of FoxP3+CD4+ regulatory T cells in inflammatory bowel disease [J].
Ban, Hiromitsu ;
Andoh, Akira ;
Shioya, Makoto ;
Nishida, Atsushi ;
Tsujikawa, Tomoyuki ;
Fujiyama, Yoshihide .
MOLECULAR MEDICINE REPORTS, 2008, 1 (05) :647-650
[3]  
Choi P, 1998, CLIN EXP IMMUNOL, V113, P317
[4]   Safety and Efficacy of Antigen-Specific Regulatory T-Cell Therapy for Patients With Refractory Crohn's Disease [J].
Desreumaux, Pierre ;
Foussat, Arnaud ;
Allez, Matthieu ;
Beaugerie, Laurent ;
Hebuterne, Xavier ;
Bouhnik, Yoram ;
Nachury, Maria ;
Brun, Valerie ;
Bastian, Herve ;
Belmonte, Nathalie ;
Ticchioni, Michel ;
Duchange, Agnes ;
Morel-Mandrino, Patricia ;
Neveu, Virginie ;
Clerget-Chossat, Nathalie ;
Forte, Miguel ;
Colombel, Jean-Frederic .
GASTROENTEROLOGY, 2012, 143 (05) :1207-+
[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]   Update on the Therapeutic Efficacy of Tregs in IBD: Thumbs up or Thumbs down? [J].
Fantini, Massimo C. ;
Monteleone, Giovanni .
INFLAMMATORY BOWEL DISEASES, 2017, 23 (10) :1682-1688
[7]  
Fuss IJ, 1996, J IMMUNOL, V157, P1261
[8]   FOXP3+T Cells and TGF-beta 1 in Colonic Mucosa of Children with Crohn's Disease [J].
Gil, Joo Hyun ;
Oh, Jung Eun ;
Seo, Jeong Wan ;
Cho, Min-Sun ;
Cho, Ky Young ;
Yoo, Eun Sun .
PEDIATRIC GASTROENTEROLOGY HEPATOLOGY & NUTRITION, 2011, 14 (03) :258-268
[9]   FOXP3+ T Regulatory Cell Modifications in Inflammatory Bowel Disease Patients Treated with Anti-TNFα Agents [J].
Guidi, Luisa ;
Felice, Carla ;
Procoli, Annabella ;
Bonanno, Giuseppina ;
Martinelli, Enrica ;
Marzo, Manuela ;
Mocci, Giammarco ;
Pugliese, Daniela ;
Andrisani, Gianluca ;
Danese, Silvio ;
De Vitis, Italo ;
Papa, Alfredo ;
Armuzzi, Alessandro ;
Rutella, Sergio .
BIOMED RESEARCH INTERNATIONAL, 2013, 2013
[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