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Published in: Autoimmunity Highlights 1/2019

Open Access 01-12-2019 | Ulcerative Colitis | Original Article

Protective effect of TSLP and IL-33 cytokines in ulcerative colitis

Authors: Sahar Tahaghoghi-Hajghorbani, Abolghasem Ajami, Saeedeh Ghorbanalipoor, Zahra Hosseini-khah, Saeid Taghiloo, Peyman Khaje-Enayati, Vahid Hosseini

Published in: Autoimmunity Highlights | Issue 1/2019

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Abstract

Purpose

Inflammatory bowel disease (IBD) primarily includes ulcerative colitis (UC) and Crohn’s disease (CD). Thymic stromal lymphopoietin (TSLP) is a cytokine produced by intestinal epithelial cells (IECs) with immunomodulatory properties that plays an important role in the development of regulatory T cell (Treg) responses and tolerance in the gut. On the other hand, IL-33 has been considered as a cytokine with two different properties, inflammatory and anti-inflammatory functions, the latter may play a protective role against chronic intestinal inflammation. In the present study, we investigated the relative gene expression levels of TSLP and IL-33 molecules in ulcerative colitis.

Methods

Patients with clinical symptoms of colitis undergoing a routine diagnostic colonoscopy were included in this study. Biopsy specimens were collected and divided into two parts. One part was fixed and processed for routine histopathological examinations and the other part was stored for RNA extraction. TSLP and IL-33 gene expression were determined using the SYBR Green qRT-PCR.

Results

The expression level of TSLP and IL-33 were significantly lower in UC patients compared with the control group. Moreover, the expressions of these cytokines were more down-regulated in severe UC patients compared with mild and moderate ones and the control group. We also showed a positive correlation between low expression of TSLP and IL-33 and the severity of UC disease.

Conclusions

In this study, we showed decreased mRNA expression levels of TSLP and IL-33 in UC patients and also a negative correlation between expression of TSLP and IL-33 and severity of UC disease.
Literature
2.
go back to reference Nazzal MF, Hazima MK, Al-AbassiAli H, Ad’hiah. Investigating the role of il31 in inflammatory bowel disease. Int J Curr Res. 2014;6(05):6768–71. Nazzal MF, Hazima MK, Al-AbassiAli H, Ad’hiah. Investigating the role of il31 in inflammatory bowel disease. Int J Curr Res. 2014;6(05):6768–71.
3.
go back to reference Peterson LW, Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol. 2014;14(3):141–53.CrossRef Peterson LW, Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol. 2014;14(3):141–53.CrossRef
4.
go back to reference Taylor BC, Zaph C, Troy AE, Du Y, Guild KJ, Comeau MR, Artis D. TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis. J Exp Med. 2009;206(3):655–67.CrossRef Taylor BC, Zaph C, Troy AE, Du Y, Guild KJ, Comeau MR, Artis D. TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis. J Exp Med. 2009;206(3):655–67.CrossRef
5.
go back to reference Rutella S, Locatelli F. Intestinal dendritic cells in the pathogenesis of inflammatory bowel disease. World J Gastroenterol. 2011;17(33):3761–75.CrossRef Rutella S, Locatelli F. Intestinal dendritic cells in the pathogenesis of inflammatory bowel disease. World J Gastroenterol. 2011;17(33):3761–75.CrossRef
6.
go back to reference Tezuka H, Ohteki T. Regulation of intestinal homeostasis by dendritic cells. Immunol Rev. 2010;234(1):247–58.CrossRef Tezuka H, Ohteki T. Regulation of intestinal homeostasis by dendritic cells. Immunol Rev. 2010;234(1):247–58.CrossRef
7.
go back to reference Maloy KJ, Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature. 2011;474(7351):298–306.CrossRef Maloy KJ, Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature. 2011;474(7351):298–306.CrossRef
8.
go back to reference Pott J, Hornef M. Innate immune signalling at the intestinal epithelium in homeostasis and disease. EMBO Rep. 2012;13(8):684–98.CrossRef Pott J, Hornef M. Innate immune signalling at the intestinal epithelium in homeostasis and disease. EMBO Rep. 2012;13(8):684–98.CrossRef
9.
go back to reference Abraham C, Medzhitov R. Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterology. 2011;140(6):1729–37.CrossRef Abraham C, Medzhitov R. Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterology. 2011;140(6):1729–37.CrossRef
10.
go back to reference Boden EK, Snapper SB. Regulatory T cells in inflammatory bowel disease. Curr Opin Gastroenterol. 2008;24(6):733–41.CrossRef Boden EK, Snapper SB. Regulatory T cells in inflammatory bowel disease. Curr Opin Gastroenterol. 2008;24(6):733–41.CrossRef
11.
go back to reference Ordonez F, Lacaille F, Canioni D, Talbotec C, Fournet JC, Cerf-Bensussan N, Goulet O, Schmitz J, Ruemmele FM. Pediatric ulcerative colitis associated with autoimmune diseases: a distinct form of inflammatory bowel disease? Inflamm Bowel Dis. 2012;18(10):1809–17.CrossRef Ordonez F, Lacaille F, Canioni D, Talbotec C, Fournet JC, Cerf-Bensussan N, Goulet O, Schmitz J, Ruemmele FM. Pediatric ulcerative colitis associated with autoimmune diseases: a distinct form of inflammatory bowel disease? Inflamm Bowel Dis. 2012;18(10):1809–17.CrossRef
12.
go back to reference Ziegler SF, Roan F, Bell BD, Stoklasek TA, Kitajima M, Han H. The biology of thymic stromal lymphopoietin (TSLP). Adv Pharmacol (San Diego, Calif). 2013;66:129.CrossRef Ziegler SF, Roan F, Bell BD, Stoklasek TA, Kitajima M, Han H. The biology of thymic stromal lymphopoietin (TSLP). Adv Pharmacol (San Diego, Calif). 2013;66:129.CrossRef
13.
go back to reference Liu YJ. TSLP in epithelial cell and dendritic cell cross talk. Adv Immunol. 2009;101:1–25.CrossRef Liu YJ. TSLP in epithelial cell and dendritic cell cross talk. Adv Immunol. 2009;101:1–25.CrossRef
14.
go back to reference Rochman Y, Spolski R, Leonard WJ. New insights into the regulation of T cells by γc family cytokines. Nat Rev Immunol. 2009;9(7):480–90.CrossRef Rochman Y, Spolski R, Leonard WJ. New insights into the regulation of T cells by γc family cytokines. Nat Rev Immunol. 2009;9(7):480–90.CrossRef
15.
go back to reference Soumelis V, Liu Y-J. Human thymic stromal lymphopoietin: a novel epithelial cell-derived cytokine and a potential key player in the induction of allergic inflammation. Springer seminars in immunopathology, vol. 34. Berlin: Springer; 2004. p. 325–33. Soumelis V, Liu Y-J. Human thymic stromal lymphopoietin: a novel epithelial cell-derived cytokine and a potential key player in the induction of allergic inflammation. Springer seminars in immunopathology, vol. 34. Berlin: Springer; 2004. p. 325–33.
16.
go back to reference Pastorelli L, De Salvo C, Cominelli MA, Vecchi M, Pizarro TT. Novel cytokine signaling pathways in inflammatory bowel disease: insight into the dichotomous functions of IL-33 during chronic intestinal inflammation. Ther Adv Gastroenterol. 2011;4(5):311–23.CrossRef Pastorelli L, De Salvo C, Cominelli MA, Vecchi M, Pizarro TT. Novel cytokine signaling pathways in inflammatory bowel disease: insight into the dichotomous functions of IL-33 during chronic intestinal inflammation. Ther Adv Gastroenterol. 2011;4(5):311–23.CrossRef
17.
go back to reference De Souza HS. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol. 2016;13(1):13.CrossRef De Souza HS. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol. 2016;13(1):13.CrossRef
18.
go back to reference Ayako K, Yagi Y, Imaeda H, Ban H, Bamba S, Tsujikawa T, Saito Y, Fujiyama Y, Andoh A. Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis. J Gastroenterol. 2010;45:999–1007.CrossRef Ayako K, Yagi Y, Imaeda H, Ban H, Bamba S, Tsujikawa T, Saito Y, Fujiyama Y, Andoh A. Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis. J Gastroenterol. 2010;45:999–1007.CrossRef
21.
go back to reference Pichery M, Mirey E, Mercier P, Lefrancais E, Dujardin A, Ortega N, Girard J-P. Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues, lymphoid organs, brain, embryos, and inflamed tissues: in situ analysis using a novel Il-33-LacZ gene trap reporter strain. J Immunol. 2012;188(7):3488–95.CrossRef Pichery M, Mirey E, Mercier P, Lefrancais E, Dujardin A, Ortega N, Girard J-P. Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues, lymphoid organs, brain, embryos, and inflamed tissues: in situ analysis using a novel Il-33-LacZ gene trap reporter strain. J Immunol. 2012;188(7):3488–95.CrossRef
22.
go back to reference Monticelli LA, Osborne LC, Noti M, Tran SV, Zaiss DM, Artis D. IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions. Proc Natl Acad Sci. 2015;112(34):10762–7.CrossRef Monticelli LA, Osborne LC, Noti M, Tran SV, Zaiss DM, Artis D. IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions. Proc Natl Acad Sci. 2015;112(34):10762–7.CrossRef
23.
go back to reference Pastorelli L, Garg RR, Hoang SB, Spina L, Mattioli B, Scarpa M, Fiocchi C, Vecchi M, Pizarro TT. Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis. Proc Natl Acad Sci. 2010;107(17):8017–22.CrossRef Pastorelli L, Garg RR, Hoang SB, Spina L, Mattioli B, Scarpa M, Fiocchi C, Vecchi M, Pizarro TT. Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis. Proc Natl Acad Sci. 2010;107(17):8017–22.CrossRef
24.
go back to reference Sponheim J, Pollheimer J, Olsen T, Balogh J, Hammarström C, Loos T, Kasprzycka M, Sørensen DR, Nilsen HR, Küchler AM. Inflammatory bowel disease-associated interleukin-33 is preferentially expressed in ulceration-associated myofibroblasts. Am J Pathol. 2010;177(6):28042815.CrossRef Sponheim J, Pollheimer J, Olsen T, Balogh J, Hammarström C, Loos T, Kasprzycka M, Sørensen DR, Nilsen HR, Küchler AM. Inflammatory bowel disease-associated interleukin-33 is preferentially expressed in ulceration-associated myofibroblasts. Am J Pathol. 2010;177(6):28042815.CrossRef
25.
go back to reference Ajduković J, Tonkić A, Salamunić I, Hozo I, Simunić M, Bonacin D. Interleukins IL-33 and IL-17/IL-A in patients with ulcerative colitis. Hepatogastroenterology. 2010;57:1442–4.PubMed Ajduković J, Tonkić A, Salamunić I, Hozo I, Simunić M, Bonacin D. Interleukins IL-33 and IL-17/IL-A in patients with ulcerative colitis. Hepatogastroenterology. 2010;57:1442–4.PubMed
26.
go back to reference Komai Koma M, Xu D, Li Y, McKenzie AN, McInnes IB, Liew FY. IL-33 is a chemoattractant for human Th2 cells. Eur J Immunol. 2007;37(10):2779–86.CrossRef Komai Koma M, Xu D, Li Y, McKenzie AN, McInnes IB, Liew FY. IL-33 is a chemoattractant for human Th2 cells. Eur J Immunol. 2007;37(10):2779–86.CrossRef
27.
go back to reference Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23(5):479–90.CrossRef Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23(5):479–90.CrossRef
28.
go back to reference Seo DH, Che X, Kwak MS, Kim S, Kim JH, Ma HW, Kim DH, Kim TI, Kim WH, Kim SW. Interleukin33 regulates intestinal inflammation by modulating macrophages in inflammatory bowel disease. Sci Rep. 2017;7(1):851.CrossRef Seo DH, Che X, Kwak MS, Kim S, Kim JH, Ma HW, Kim DH, Kim TI, Kim WH, Kim SW. Interleukin33 regulates intestinal inflammation by modulating macrophages in inflammatory bowel disease. Sci Rep. 2017;7(1):851.CrossRef
29.
go back to reference Kobori A, Yagi Y, Imaeda H, Ban H, Bamba S, Tsujikawa T, Saito Y, Fujiyama Y, Andoh A. Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis. J Gastroenterol. 2010;45(10):999–1007.CrossRef Kobori A, Yagi Y, Imaeda H, Ban H, Bamba S, Tsujikawa T, Saito Y, Fujiyama Y, Andoh A. Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis. J Gastroenterol. 2010;45(10):999–1007.CrossRef
30.
go back to reference Fuss IJ. Is the Th1/Th2 paradigm of immune regulation applicable to IBD? Inflamm Bowel Dis. 2008;14:S110–2.CrossRef Fuss IJ. Is the Th1/Th2 paradigm of immune regulation applicable to IBD? Inflamm Bowel Dis. 2008;14:S110–2.CrossRef
31.
go back to reference Park JH, Jeong DY, Peyrin-Biroulet L, Eisenhut M, Shin JI. Insight into the role of TSLP in inflammatory bowel diseases. Autoimmun Rev. 2017;16(1):55–63.CrossRef Park JH, Jeong DY, Peyrin-Biroulet L, Eisenhut M, Shin JI. Insight into the role of TSLP in inflammatory bowel diseases. Autoimmun Rev. 2017;16(1):55–63.CrossRef
32.
go back to reference Beltrán CJ, Núñez LE, Díaz Jiménez D, Farfan N, Candia E, Heine C, Lopez F, González MJ, Quera R, Hermoso MA. Characterization of the novel ST2/IL33 system in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2010;16(7):1097–107.CrossRef Beltrán CJ, Núñez LE, Díaz Jiménez D, Farfan N, Candia E, Heine C, Lopez F, González MJ, Quera R, Hermoso MA. Characterization of the novel ST2/IL33 system in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2010;16(7):1097–107.CrossRef
Metadata
Title
Protective effect of TSLP and IL-33 cytokines in ulcerative colitis
Authors
Sahar Tahaghoghi-Hajghorbani
Abolghasem Ajami
Saeedeh Ghorbanalipoor
Zahra Hosseini-khah
Saeid Taghiloo
Peyman Khaje-Enayati
Vahid Hosseini
Publication date
01-12-2019
Publisher
Springer International Publishing
Published in
Autoimmunity Highlights / Issue 1/2019
Print ISSN: 2038-0305
Electronic ISSN: 2038-3274
DOI
https://doi.org/10.1186/s13317-019-0110-z

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