Anti-Inflammatory Effect of IL-37-Producing T-Cell Population in DSS-Induced Chronic Inflammatory Bowel Disease in Mice
Abstract
:1. Introduction
2. Results
2.1. Transgenic IL-37 Expression Alleviates DSS (Dextran Sodium Sulfate)-Induced Colitis in Mice
2.2. IL-37 Expression Is Inducible and Inhibits the Colonic Proinflammatory Cytokines
2.3. IL-37-Producing T-Cell Population in Chronic Colitis
2.4. Anti-Inflammatory Role of IL-37-Producing T-Cells in DSS-Induced Colitis
3. Discussion
4. Materials and Methods
4.1. Mice
4.2. DSS-Induced Chronic Colitis
4.3. Assessment of Disease Activity Index
4.4. Evaluation of Colonic Inflammation and Histology
4.5. RT-qPCR
4.6. Immunoblotting
4.7. ELISA
4.8. Isolation of Splenocytes and Mesenteric Lymph Node Cells (MLNCs) from Colonic Tissue
4.9. Flow Cytometry
4.10. Cell Sorting and Adoptive Cell Transfer
4.11. Statistical Analysis
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- De Lange, K.M.; Barrett, J.C. Understanding inflammatory bowel disease via immunogenetics. J. Autoimmun. 2015, 64, 91–100. [Google Scholar] [CrossRef] [PubMed]
- Sheehan, D.; Moran, C.; Shanahan, F. The microbiota in inflammatory bowel disease. J. Gastroenterol. 2015, 50, 495–507. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kabat, A.M.; Pott, J.; Maloy, K.J. The mucosal immune system and its regulation by autophagy. Front. Immunol. 2016, 7, 240. [Google Scholar] [CrossRef] [PubMed]
- Choy, M.C.; Visvanathan, K.; De Cruz, P. An Overview of the Innate and Adaptive Immune System in Inflammatory Bowel Disease. Inflamm. Bowel Dis. 2017, 23, 2–13. [Google Scholar] [CrossRef] [PubMed]
- Camelo, A.; Barlow, J.L.; Drynan, L.F.; Neill, D.R.; Ballantyne, S.J.; Wong, S.H.; Pannell, R.; Gao, W.; Wrigley, K.; Sprenkle, J.; et al. Blocking IL-25 signalling protects against gut inflammation in a type-2 model of colitis by suppressing nuocyte and NKT derived IL-13. J. Gastroenterol. 2012, 47, 1198–1211. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Waddell, A.; Vallance, J.E.; Moore, P.D.; Hummel, A.T.; Wu, D.; Shanmukhappa, S.K.; Fei, L.; Washington, M.K.; Minar, P.; Coburn, L.A.; et al. IL-33 Signaling Protects from Murine Oxazolone Colitis by Supporting Intestinal Epithelial Function. Inflamm. Bowel Dis. 2015, 21, 2737–2746. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Globig, A.M.; Hennecke, N.; Martin, B.; Seidl, M.; Ruf, G.; Hasselblatt, P.; Thimme, R.; Bengsch, B. Comprehensive intestinal T helper cell profiling reveals specific accumulation of IFN-γ + IL-17+ coproducing CD4+ T-cells in active inflammatory bowel disease. Inflamm. Bowel Dis. 2014, 20, 2321–2329. [Google Scholar] [CrossRef] [PubMed]
- Monteleone, I.; Pallone, F.; Monteleone, G. Th17-related cytokines: New players in the control of chronic intestinal inflammation. BMC Med. 2011, 9, 122. [Google Scholar] [CrossRef]
- Bettelli, E.; Korn, T.; Oukka, M.; Kuchroo, V.K. Induction and effector functions of Th17 cells. Nature 2008, 453, 1051–1057. [Google Scholar] [CrossRef]
- Schiering, C.; Krausgruber, T.; Chomka, A.; Frohlich, A.; Adelmann, K.; Wohlfert, E.A.; Pott, J.; Griseri, T.; Bollrath, J.; Hegazy, A.N.; et al. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature 2014, 513, 564–568. [Google Scholar] [CrossRef] [Green Version]
- Harrison, O.J.; Srinivasan, N.; Pott, J.; Schiering, C.; Krausgruber, T.; Ilott, N.E.; Maloy, K.J. Epithelial-derived IL-18 regulates Th17 cell differentiation and Foxp3+ Treg cell function in the intestine. Mucosal Immunol. 2015, 8, 1226–1236. [Google Scholar] [CrossRef] [PubMed]
- Nold, M.F.; Nold-Petry, C.A.; Zepp, J.A.; Palmer, B.E.; Bufler, P.; Dinarello, C.A. IL-37 is a fundamental inhibitor of innate immunity. Nat. Immunol. 2010, 11, 1014–1022. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, B.; Meng, K.; Ji, Q.; Cheng, M.; Yu, K.; Zhao, X.; Tony, H.; Liu, Y.; Zhou, Y.; Chang, C.; et al. Interleukin-37 ameliorates myocardial ischaemia/reperfusion injury in mice. Clin. Exp. Immunol. 2014, 176, 438–451. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Coll-Miro, M.; Francos-Quijorna, I.; Santos-Nogueira, E.; Torres-Espin, A.; Bufler, P.; Dinarello, C.A.; Lopez-Vales, R. Beneficial effects of IL-37 after spinal cord injury in mice. Proc. Natl. Acad. Sci. USA 2016, 113, 1411–1416. [Google Scholar] [CrossRef]
- Luo, Y.; Cai, X.; Liu, S.; Wang, S.; Nold-Petry, C.A.; Nold, M.F.; Bufler, P.; Norris, D.; Dinarello, C.A.; Fujita, M. Suppression of antigen-specific adaptive immunity by IL-37 via induction of tolerogenic dendritic cells. Proc. Natl. Acad. Sci. USA 2014, 111, 15178–15183. [Google Scholar] [CrossRef] [Green Version]
- Moretti, S.; Bozza, S.; Oikonomou, V.; Renga, G.; Casagrande, A.; Iannitti, R.G.; Puccetti, M.; Garlanda, C.; Kim, S.; Li, S.; et al. IL-37 inhibits inflammasome activation and disease severity in murine aspergillosis. PLoS Pathog. 2014, 10, e1004462. [Google Scholar] [CrossRef] [Green Version]
- Fonseca-Camarillo, G.; Furuzawa-Carballeda, J.; Yamamoto-Furusho, J.K. Interleukin 35 (IL-35) and IL-37: Intestinal and peripheral expression by T and B regulatory cells in patients with Inflammatory Bowel Disease. Cytokine 2015, 75, 389–402. [Google Scholar] [CrossRef]
- Imaeda, H.; Takahashi, K.; Fujimoto, T.; Kasumi, E.; Ban, H.; Bamba, S.; Sonoda, H.; Shimizu, T.; Fujiyama, Y.; Andoh, A. Epithelial expression of interleukin-37B in inflammatory bowel disease. Clin. Exp. Immunol. 2013, 172, 410–416. [Google Scholar] [CrossRef]
- McNamee, E.N.; Masterson, J.C.; Jedlicka, P.; McManus, M.; Grenz, A.; Collins, C.B.; Nold, M.F.; Nold-Petry, C.; Bufler, P.; Dinarello, C.A.; et al. Interleukin 37 expression protects mice from colitis. Proc. Natl. Acad. Sci. USA 2011, 108, 16711–16716. [Google Scholar] [CrossRef] [Green Version]
- Mayne, C.G.; Williams, C.B. Induced and natural regulatory T-cells in the development of inflammatory bowel disease. Inflamm. Bowel Dis. 2013, 19, 1772–1788. [Google Scholar] [CrossRef]
- Hoeke, G.; Khedoe, P.; van Diepen, J.A.; Pike-Overzet, K.; van de Ven, B.; Vazirpanah, N.; Mol, I.; Hiemstra, P.S.; Staal, F.J.T.; Stienstra, R.; et al. The Effects of Selective Hematopoietic Expression of Human IL-37 on Systemic Inflammation and Atherosclerosis in LDLr-Deficient Mice. Int. J. Mol. Sci. 2017, 18, 1672. [Google Scholar] [CrossRef] [PubMed]
- McCurdy, S.; Baumer, Y.; Toulmin, E.; Lee, B.H.; Boisvert, W.A. Macrophage-specific expression of IL-37 in hyperlipidemic mice attenuates atherosclerosis. J. Immunol. 2017, 199, 3604–3613. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Ueno, A.; Fort Gasia, M.; Luider, J.; Wang, T.; Hirota, C.; Jijon, H.B.; Deane, M.; Tom, M.; Chan, R.; et al. Profiles of lamina propria T helper cell subsets discriminate between ulcerative colitis and crohn’s disease. Inflamm. Bowel Dis. 2016, 22, 1779–1792. [Google Scholar] [CrossRef] [PubMed]
- Eichele, D.D.; Kharbanda, K.K. Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis. World J. Gastroenterol. 2017, 23, 6016–6029. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McLean, L.P.; Cross, R.K.; Shea-Donohue, T. Combined blockade of IL-17A and IL-17F may prevent the development of experimental colitis. Immunotherapy 2013, 5, 923–925. [Google Scholar] [CrossRef] [Green Version]
- Galvez, J. Role of Th17 cells in the pathogenesis of human IBD. ISRN Inflamm. 2014, 2014, 928461. [Google Scholar] [CrossRef]
- Yamada, A.; Arakaki, R.; Saito, M.; Tsunematsu, T.; Kudo, Y.; Ishimaru, N. Role of regulatory T-cell in the pathogenesis of inflammatory bowel disease. World J. Gastroenterol. 2016, 22, 2195–2205. [Google Scholar] [CrossRef]
- Kersting, S.; Behrendt, V.; Kersting, J.; Reinecke, K.; Hilgert, C.; Stricker, I.; Herdegen, T.; Janot, M.S.; Uhl, W.; Chromik, A.M. The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium. J. Inflamm. Res. 2013, 6, 71–81. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yonamine, Y.; Watanabe, M.; Kinjo, F.; Hibi, T. Generation of MHC class I-restricted cytotoxic T-cell lines and clones against colonic epithelial cells from ulcerative colitis. J. Clin. Immunol. 1999, 19, 77–85. [Google Scholar] [CrossRef]
- Smith, D.E.; Renshaw, B.R.; Ketchem, R.R.; Kubin, M.; Garka, K.E.; Sims, J.E. Four new members expand the interleukin-1 superfamily. J. Biol. Chem. 2000, 275, 1169–1175. [Google Scholar] [CrossRef]
- Davis, C.J.; Zielinski, M.R.; Dunbrasky, D.; Taishi, P.; Dinarello, C.A.; Krueger, J.M. Interleukin 37 expression in mice alters sleep responses to inflammatory agents and influenza virus infection. Neurobiol. Sleep Circad. Rhyth. 2017, 3, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Boraschi, D.; Lucchesi, D.; Hainzl, S.; Leitner, M.; Maier, E.; Mangelberger, D.; Oostingh, G.J.; Pfaller, T.; Pixner, C.; Posselt, G.; et al. IL-37: A new anti-inflammatory cytokine of the IL-1 family. Eur. Cytokine Netw. 2011, 22, 127–147. [Google Scholar] [PubMed]
- Li, Y.; Wang, Z.; Yu, T.; Chen, B.; Zhang, J.; Huang, K.; Huang, Z. Increased expression of IL-37 in patients with Graves’ disease and its contribution to suppression of proinflammatory cytokines production in peripheral blood mononuclear cells. PLoS ONE 2014, 9, e107183. [Google Scholar] [CrossRef] [PubMed]
- Farrokhi, M.; Rezaei, A.; Amani-Beni, A.; Etemadifar, M.; Kouchaki, E.; Zahedi, A. Increased serum level of IL-37 in patients with multiple sclerosis and neuromyelitis optica. Acta Neurol. Belgica 2015, 115, 609–614. [Google Scholar] [CrossRef] [PubMed]
- Ye, L.; Jiang, B.; Deng, J.; Du, J.; Xiong, W.; Guan, Y.; Wen, Z.; Huang, K.; Huang, Z. IL-37 alleviates rheumatoid arthritis by suppressing IL-17 and IL-17-triggering cytokine production and limiting Th17 cell proliferation. J. Immunol. 2015, 194, 5110–5119. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Zhang, Z.X.; Lian, D.; Haig, A.; Bhattacharjee, R.N.; Jevnikar, A.M. IL-37 inhibits IL-18-induced tubular epithelial cell expression of pro-inflammatory cytokines and renal ischemia-reperfusion injury. Kidney Int. 2015, 87, 396–408. [Google Scholar] [CrossRef]
- Cooper, H.S.; Murthy, S.N.; Shah, R.S.; Sedergran, D.J. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab. Investig. 1993, 69, 238–249. [Google Scholar]
- De Bruyn, M.; Breynaert, C.; Arijs, I.; de Hertogh, G.; Geboes, K.; Thijs, G.; Matteoli, G.; Hu, J.; Van Damme, J.; Arnold, B.; et al. Inhibition of gelatinase B/MMP-9 does not attenuate colitis in murine models of inflammatory bowel disease. Nat. Commun. 2017, 8, 15384. [Google Scholar] [CrossRef] [Green Version]
- Perrier, C.; de Hertogh, G.; Cremer, J.; Vermeire, S.; Rutgeerts, P.; Van Assche, G.; Szymkowski, D.E.; Ceuppens, J.L. Neutralization of membrane TNF, but not soluble TNF, is crucial for the treatment of experimental colitis. Inflamm. Bowel Dis. 2013, 19, 246–253. [Google Scholar] [CrossRef]
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Chen, Z.; Wang, S.; Li, L.; Huang, Z.; Ma, K. Anti-Inflammatory Effect of IL-37-Producing T-Cell Population in DSS-Induced Chronic Inflammatory Bowel Disease in Mice. Int. J. Mol. Sci. 2018, 19, 3884. https://doi.org/10.3390/ijms19123884
Chen Z, Wang S, Li L, Huang Z, Ma K. Anti-Inflammatory Effect of IL-37-Producing T-Cell Population in DSS-Induced Chronic Inflammatory Bowel Disease in Mice. International Journal of Molecular Sciences. 2018; 19(12):3884. https://doi.org/10.3390/ijms19123884
Chicago/Turabian StyleChen, Zhangbo, Shijun Wang, Lingyun Li, Zhong Huang, and Ke Ma. 2018. "Anti-Inflammatory Effect of IL-37-Producing T-Cell Population in DSS-Induced Chronic Inflammatory Bowel Disease in Mice" International Journal of Molecular Sciences 19, no. 12: 3884. https://doi.org/10.3390/ijms19123884