Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
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Activation and Recruitment of Regulatory T Cells via Chemokine Receptor Activation in Trichinella spiralis-Infected Mice

  • Ahn, Jeong-Bin (Department of Parasitology, School of Medicine, Pusan National University) ;
  • Kang, Shin Ae (Department of Parasitology, School of Medicine, Pusan National University) ;
  • Kim, Dong-Hee (Department of Nursing, College of Nursing, Pusan National University) ;
  • Yu, Hak Sun (Department of Parasitology, School of Medicine, Pusan National University)
  • Received : 2016.01.02
  • Accepted : 2016.03.15
  • Published : 2016.04.30
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Abstract

As most infections by the helminth parasite elicit the recruitment of $CD4^+CD25^+Foxp3^+$ T ($T_{reg}$) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated $T_{reg}$ cells, we compared the expression levels of $T_{reg}$ cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of $T_{reg}$ cells was monitored using GFP-coded Foxp3 transgenic mice. In mice at 1 week after Trichinella spiralis infection, the number of activated $T_{reg}$ cells was higher than in the control group. In mice at 2 weeks after infection, there was a significant increase in the number of cells expressing Foxp3 and CTLA-4 when compared to the control group and mice at 1 week after infection. At 4 weeks after infection, T. spiralis was easily identifiable in nurse cells in mouse muscles. In the intestine, the expression of Gzmb and Klrg1 decreased over time and that of Capg remained unchanged for the first and second week, then decreased in the 4th week. However, in the muscles, the expression of most chemokine genes was increased due to T. spiralis infection, in particular the expression levels of Gzmb, OX40, and CTLA-4 increased until week 4. In addition, increased gene expression of all chemokine receptors in muscle, CXCR3, CCR4, CCR5, CCR9, and CCR10, was observed up until the 4th week. In conclusion, various chemokine receptors showed increased expressions combined with recruitment of $T_{reg}$ cells in the muscle tissue.

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References

  1. Julia V, Macia L, Dombrowicz D. The impact of diet on asthma and allergic diseases. Nat Rev Immunol 2015; 15: 308-322. https://doi.org/10.1038/nri3830
  2. Loke P, Lim YA. Helminths and the microbiota: parts of the hygiene hypothesis. Parasite Immunol 2015; 37: 314-323. https://doi.org/10.1111/pim.12193
  3. Flohr C, Quinnell RJ, Britton J. Do helminth parasites protect against atopy and allergic disease? Clin Exp Allergy 2009; 39: 20-32. https://doi.org/10.1111/j.1365-2222.2008.03134.x
  4. Fogarty AW. What have studies of non-industrialized countries told us about the cause of allergic disease? Clin Exp Allergy 2015; 45: 87-93. https://doi.org/10.1111/cea.12339
  5. Zaph C, Cooper PJ, Harris NL. Mucosal immune responses following intestinal nematode infection. Parasite Immunol 2014; 36: 439-452. https://doi.org/10.1111/pim.12090
  6. Xiong N, Fu Y, Hu S, Xia M, Yang J. CCR10 and its ligands in regulation of epithelial immunity and diseases. Protein Cell 2012; 3: 571-580. https://doi.org/10.1007/s13238-012-2927-3
  7. Taylor MD, van der Werf N, Maizels RM. T cells in helminth infection: the regulators and the regulated. Trends Immunol 2012; 33: 181-189. https://doi.org/10.1016/j.it.2012.01.001
  8. Peterson RA. Regulatory T-cells: diverse phenotypes integral to immune homeostasis and suppression. Toxicol Pathol 2012; 40: 186-204. https://doi.org/10.1177/0192623311430693
  9. Askenasy N, Kaminitz A, Yarkoni S. Mechanisms of T regulatory cell function. Autoimmun Rev 2008; 7: 370-375. https://doi.org/10.1016/j.autrev.2008.03.001
  10. Kang SA, Cho MK, Park MK, Kim DH, Hong YC, Lee YS, Cha HJ, Ock MS, Yu HS. Alteration of helper T-cell related cytokine production in splenocytes during Trichinella spiralis infection. Vet Parasitol 2012; 186: 319-327. https://doi.org/10.1016/j.vetpar.2011.12.002
  11. Park HK, Cho MK, Choi SH, Kim YS, Yu HS. Trichinella spiralis: infection reduces airway allergic inflammation in mice. Exp Parasitol 2011; 127: 539-544. https://doi.org/10.1016/j.exppara.2010.10.004
  12. Cho MK, Park MK, Kang SA, Choi SH, Ahn SC, Yu HS. Trichinella spiralis infection suppressed gut inflammation with $CD4^+CD25^+Foxp3^+$ T cell recruitment. Korean J Parasitol 2012; 50: 385-390. https://doi.org/10.3347/kjp.2012.50.4.385
  13. Kang SA, Park MK, Cho MK, Park SK, Jang MS, Yang BG, Jang MH, Kim DH, Yu HS. Parasitic nematode-induced $CD4^+Foxp3^+$ T cells can ameliorate allergic airway inflammation. PLoS Negl Trop Dis 2014; 8: e3410. https://doi.org/10.1371/journal.pntd.0003410
  14. Radovic I, Gruden-Movsesijan A, Ilic N, Cvetkovic J, Mojsilovic S, Devic M, Sofronic-Milosavljevic L. Immunomodulatory effects of Trichinella spiralis-derived excretory-secretory antigens. Immunol Res 2015; 61: 312-325. https://doi.org/10.1007/s12026-015-8626-4
  15. Campbell WC. Trichinella and trichinosis. New York, USA. Plenum Press. 1983, p 581.
  16. Shevach EM. Mechanisms of $Foxp3^+$ T regulatory cell-mediated suppression. Immunity 2009; 30: 636-645. https://doi.org/10.1016/j.immuni.2009.04.010
  17. Ephrem A, Epstein AL, Stephens GL, Thornton AM, Glass D, Shevach EM. Modulation of $T_{reg}$ cells/T effector function by GITR signaling is context-dependent. Eur J Immunol 2013; 43: 2421-2429. https://doi.org/10.1002/eji.201343451
  18. Xiao X, Gong W, Demirci G, Liu W, Spoerl S, Chu X, Bishop DK, Turka LA, Li XC. New insights on OX40 in the control of T cell immunity and immune tolerance in vivo. J Immunol 2012; 188: 892-901. https://doi.org/10.4049/jimmunol.1101373
  19. Loebbermann J, Thornton H, Durant L, Sparwasser T, Webster KE, Sprent J, Culley FJ, Johansson C, Openshaw PJ. Regulatory T cells expressing granzyme B play a critical role in controlling lung inflammation during acute viral infection. Mucosal Immunol 2012; 5: 161-172. https://doi.org/10.1038/mi.2011.62
  20. Tai XG, Van Laethem F, Pobezinsky L, Guinter T, Sharrow SO, Adams A, Granger L, Kruhlak M, Lindsten T, Thompson CB, Feigenbaum L, Singer A. Basis of CTLA-4 function in regulatory and conventional CD4+ T cells. Blood 2012; 119: 5155-5163. https://doi.org/10.1182/blood-2011-11-388918
  21. Velavan TP, Ojurongbe O. Regulatory T cells and parasites. J Biomed Biotechnol 2011; 2011: 520940.
  22. Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol 2016; 39: 98-106. https://doi.org/10.1097/COC.0000000000000239
  23. Hahn SA, Stahl HF, Becker C, Correll A, Schneider FJ, Tuettenberg A, Jonuleit H. Soluble GARP has potent antiinflammatory and immunomodulatory impact on human CD4+ T cells. Blood 2013; 122: 1182-1191. https://doi.org/10.1182/blood-2012-12-474478
  24. Sun L, Yi S, O'Connell PJ. Foxp3 regulates human natural $CD4^+CD25^+$ regulatory T-cell-mediated suppression of xenogeneic response. Xenotransplantation 2010; 17: 121-130. https://doi.org/10.1111/j.1399-3089.2010.00571.x
  25. Mahmud SA, Manlove LS, Schmitz HM, Xing Y, Wang Y, Owen DL, Schenkel JM, Boomer JS, Green JM, Yagita H, Chi H, Hogquist KA, Farrar MA. Costimulation via the tumor-necrosis factor receptor superfamily couples TCR signal strength to the thymic differentiation of regulatory T cells. Nat Immunol 2014; 15: 473-481. https://doi.org/10.1038/ni.2849
  26. Shevach EM, DiPaolo RA, Andersson J, Zhao DM, Stephens GL, Thornton AM. The lifestyle of naturally occurring $CD4^+\;CD25^+\;Foxp3^+$ regulatory T cells. Immunol Rev 2006; 212: 60-73. https://doi.org/10.1111/j.0105-2896.2006.00415.x
  27. Lange C, Scholl M, Melms A, Bischof F. CD62L(high) $T_{reg}$ cells with superior immunosuppressive properties accumulate within the CNS during remissions of EAE. Brain Behav Immun 2011; 25: 120-126. https://doi.org/10.1016/j.bbi.2010.09.004
  28. Bromley SK, Mempel TR, Luster AD. Orchestrating the orchestrators: chemokines in control of T cell traffic. Nat Immunol 2008; 9: 970-980. https://doi.org/10.1038/ni.f.213
  29. Homey B, Alenius H, Muller A, Soto H, Bowman EP, Yuan W, McEvoy L, Lauerma AI, Assmann T, Bünemann E, Lehto M, Wolff H, Yen D, Marxhausen H, To W, Sedgwick J, Ruzicka T, Lehmann P, Zlotnik A. CCL27-CCR10 interactions regulate T cell-mediated skin inflammation. Nat Med 2002; 8: 157-165. https://doi.org/10.1038/nm0202-157
  30. Eksteen B, Miles A, Curbishley SM, Tselepis C, Grant AJ, Walker LS, Adams DH. Epithelial inflammation is associated with CCL28 production and the recruitment of regulatory T cells expressing CCR10. J Immunol 2006; 177: 593-603. https://doi.org/10.4049/jimmunol.177.1.593
  31. English K, Brady C, Corcoran P, Cassidy JP, Mahon BP. Inflammation of the respiratory tract is associated with CCL28 and CCR10 expression in a murine model of allergic asthma. Immunol Lett 2006; 103: 92-100. https://doi.org/10.1016/j.imlet.2005.09.011
  32. Castelletti E, Lo Caputo S, Kuhn L, Borelli M, Gajardo J, Sinkala M, Trabattoni D, Kankasa C, Lauri E, Clivio A, Piacentini L, Bray DH, Aldrovandi GM, Thea DM, Veas F, Nebuloni M, Mazzotta F, Clerici M. The mucosae-associated epithelial chemokine (MEC/CCL28) modulates immunity in HIV infection. PLoS One 2007; 2: e969. https://doi.org/10.1371/journal.pone.0000969
  33. Wang Z, Pratts SG, Zhang H, Spencer PJ, Yu R, Tonsho M, Shah JA, Tanabe T, Powell HR, Huang CA, Madsen JC, Sachs DH, Wang Z. $T_{reg}$ depletion in non-human primates using a novel diphtheria toxin-based anti-human CCR4 immunotoxin. Mol Oncol 2016; 10: 553-565. https://doi.org/10.1016/j.molonc.2015.11.008
  34. Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, Ezoe S, Kanakura Y, Sato E, Fukumori Y, Karbach J, Jager E, Sakaguchi S. Anti-CCR4 mAb selectively depletes effector-type $FoxP3^+CD4^+$ regulatory T cells, evoking antitumor immune responses in humans. Proc Natl Acad Sci USA 2013; 110: 17945-17950. https://doi.org/10.1073/pnas.1316796110
  35. Kurose K, Ohue Y, Sato E, Yamauchi A, Eikawa S, Isobe M, Nishio Y, Uenaka A, Oka M, Nakayama E. Increase in activated $T_{reg}$ in TIL in lung cancer and in vitro depletion of $T_{reg}$ by ADCC using an antihuman CCR4 mAb (KM2760). J Thorac Oncol 2015; 10: 74-83. https://doi.org/10.1097/JTO.0000000000000364
  36. Dobaczewski M, Xia Y, Bujak M, Gonzalez-Quesada C, Frangogiannis NG. CCR5 signaling suppresses inflammation and reduces adverse remodeling of the infarcted heart, mediating recruitment of regulatory T cells. Am J Pathol 2010; 176: 2177-2187. https://doi.org/10.2353/ajpath.2010.090759
  37. Hasegawa H, Inoue A, Kohno M, Lei J, Miyazaki T, Yoshie O, Nose M, Yasukawa M. Therapeutic effect of CXCR3-expressing regulatory T cells on liver, lung and intestinal damages in a murine acute GVHD model. Gene Ther 2008; 15: 171-182. https://doi.org/10.1038/sj.gt.3303051
  38. Evans-Marin HL, Cao AT, Yao S, Chen F, He C, Liu H, Wu W, Gonzalez MG, Dann SM, Cong Y. Unexpected regulatory role of CCR9 in regulatory T cell development. PLoS One 2015; 10: e0134100. https://doi.org/10.1371/journal.pone.0134100
  39. Wermers JD, McNamee EN, Wurbel MA, Jedlicka P, Rivera-Nieves J. The chemokine receptor CCR9 is required for the T-cell-mediated regulation of chronic ileitis in mice. Gastroenterology 2011; 140: 1526-1535.e3. https://doi.org/10.1053/j.gastro.2011.01.044

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