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

Overview

Journal J Korean Med Sci

Specialty General Medicine

Date 2018 Dec 26

PMID 30584414

Citations 18

Authors

Jinhee Cho

Sorina Kim

DA Hee Yang

Juyeon Lee

Kyeong Won Park

Junyong Go

Chang-Lim Hyun

Youngheun Jee

Ki Soo Kang

Affiliations

Soon will be listed here.

Abstract

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-RORγt antibodies. Serum levels of cytokines were analyzed using a multiplex assay covering interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-17A/F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon (IFN)-γ, soluble CD40L, and tumor necrosis factor-α.

Results: FOXP3 Treg cells in the lamina propria (LP) of terminal ileum of patients with Crohn's disease were significantly ( < 0.05) higher than those in the healthy controls. RORγt 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-γ (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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References

Matsuura T, West G, Levine A, Fiocchi C . Selective resistance of mucosal T-cell activation to immunosuppression in Crohn's disease. Dig Liver Dis. 2000; 32(6):484-94. DOI: 10.1016/s1590-8658(00)80005-5. View

Makita S, Kanai T, Oshima S, Uraushihara K, Totsuka T, Sawada T . CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells. J Immunol. 2004; 173(5):3119-30. DOI: 10.4049/jimmunol.173.5.3119. View

Mikhalkevich N, Becknell B, Caligiuri M, Bates M, Harvey R, Zheng W . Responsiveness of naive CD4 T cells to polarizing cytokine determines the ratio of Th1 and Th2 cell differentiation. J Immunol. 2006; 176(3):1553-60. DOI: 10.4049/jimmunol.176.3.1553. View

Reinisch W, Hommes D, Van Assche G, Colombel J, Gendre J, Oldenburg B . A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease. Gut. 2006; 55(8):1138-44. PMC: 1856289. DOI: 10.1136/gut.2005.079434. View

Yu Q, Saruta M, Avanesyan A, Fleshner P, Banham A, Papadakis K . Expression and functional characterization of FOXP3+ CD4+ regulatory T cells in ulcerative colitis. Inflamm Bowel Dis. 2007; 13(2):191-9. DOI: 10.1002/ibd.20053. View

Saruta M, Yu Q, Fleshner P, Mantel P, Schmidt-Weber C, Banham A . Characterization of FOXP3+CD4+ regulatory T cells in Crohn's disease. Clin Immunol. 2007; 125(3):281-90. DOI: 10.1016/j.clim.2007.08.003. View

Sakuraba A, Sato T, Kamada N, Kitazume M, Sugita A, Hibi T . Th1/Th17 immune response is induced by mesenteric lymph node dendritic cells in Crohn's disease. Gastroenterology. 2009; 137(5):1736-45. DOI: 10.1053/j.gastro.2009.07.049. View

Abraham C, Cho J . Inflammatory bowel disease. N Engl J Med. 2009; 361(21):2066-78. PMC: 3491806. DOI: 10.1056/NEJMra0804647. View

Eastaff-Leung N, Mabarrack N, Barbour A, Cummins A, Barry S . Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease. J Clin Immunol. 2009; 30(1):80-9. DOI: 10.1007/s10875-009-9345-1. View

10.

Pastorelli L, Garg R, Hoang S, Spina L, Mattioli B, Scarpa M . Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis. Proc Natl Acad Sci U S A. 2010; 107(17):8017-22. PMC: 2867895. DOI: 10.1073/pnas.0912678107. View

11.

Ban H, Andoh A, Shioya M, Nishida A, Tsujikawa T, Fujiyama Y . Increased number of FoxP3+CD4+ regulatory T cells in inflammatory bowel disease. Mol Med Rep. 2011; 1(5):647-50. DOI: 10.3892/mmr_00000006. View

12.

Strober W, Fuss I . Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology. 2011; 140(6):1756-1767. PMC: 3773507. DOI: 10.1053/j.gastro.2011.02.016. View

13.

Hueber W, Sands B, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins P . 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. Gut. 2012; 61(12):1693-700. PMC: 4902107. DOI: 10.1136/gutjnl-2011-301668. View

14.

Lord J, Valliant-Saunders K, Hahn H, Thirlby R, Ziegler S . Paradoxically increased FOXP3+ T cells in IBD do not preferentially express the isoform of FOXP3 lacking exon 2. Dig Dis Sci. 2012; 57(11):2846-55. PMC: 3482978. DOI: 10.1007/s10620-012-2292-3. View

15.

Desreumaux P, Foussat A, Allez M, Beaugerie L, Hebuterne X, Bouhnik Y . Safety and efficacy of antigen-specific regulatory T-cell therapy for patients with refractory Crohn's disease. Gastroenterology. 2012; 143(5):1207-1217.e2. DOI: 10.1053/j.gastro.2012.07.116. View

16.

Guidi L, Felice C, Procoli A, Bonanno G, Martinelli E, Marzo M . FOXP3⁺ T regulatory cell modifications in inflammatory bowel disease patients treated with anti-TNFα agents. Biomed Res Int. 2013; 2013:286368. PMC: 3766994. DOI: 10.1155/2013/286368. View

17.

Ueno A, Jijon H, Chan R, Ford K, Hirota C, Kaplan G . Increased prevalence of circulating novel IL-17 secreting Foxp3 expressing CD4+ T cells and defective suppressive function of circulating Foxp3+ regulatory cells support plasticity between Th17 and regulatory T cells in inflammatory bowel disease.... Inflamm Bowel Dis. 2013; 19(12):2522-34. DOI: 10.1097/MIB.0b013e3182a85709. View

18.

Shen X, Du J, Guan W, Zhao Y . The balance of intestinal Foxp3+ regulatory T cells and Th17 cells and its biological significance. Expert Rev Clin Immunol. 2014; 10(3):353-62. DOI: 10.1586/1744666X.2014.882232. View

19.

Neurath M . Cytokines in inflammatory bowel disease. Nat Rev Immunol. 2014; 14(5):329-42. DOI: 10.1038/nri3661. View

20.

Tangye S . Advances in IL-21 biology - enhancing our understanding of human disease. Curr Opin Immunol. 2015; 34:107-15. DOI: 10.1016/j.coi.2015.02.010. View