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Martins LMS, Perez MM, Pereira CA, et al. Interleukin-23 promotes intestinal T helper type17 immunity and ameliorates obesity-associated metabolic syndrome in a murine high-fat diet model. Immunology. 2018;doi: 10.1111/imm.12946.
Martins, L. M. S., Perez, M. M., Pereira, C. A., Costa, F. R. C., Dias, M. S., Tostes, R. C., Ramos, S. G., de Zoete, M. R., Ryffel, B., Silva, J. S., & Carlos, D. (2018). Interleukin-23 promotes intestinal T helper type17 immunity and ameliorates obesity-associated metabolic syndrome in a murine high-fat diet model. Immunology, . https://doi.org/10.1111/imm.12946
Martins, Larissa M S, et al. "Interleukin-23 promotes intestinal T helper type17 immunity and ameliorates obesity-associated metabolic syndrome in a murine high-fat diet model." Immunology vol. (2018). doi: https://doi.org/10.1111/imm.12946
Martins LMS, Perez MM, Pereira CA, Costa FRC, Dias MS, Tostes RC, Ramos SG, de Zoete MR, Ryffel B, Silva JS, Carlos D. Interleukin-23 promotes intestinal T helper type17 immunity and ameliorates obesity-associated metabolic syndrome in a murine high-fat diet model. Immunology. 2018 May 02; doi: 10.1111/imm.12946. Epub 2018 May 02. PMID: 29722014; PMCID: PMC6050211.
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Immunology. 2018 May 02; doi: 10.1111/imm.12946. Epub 2018 May 02.

Interleukin-23 promotes intestinal T helper type17 immunity and ameliorates obesity-associated metabolic syndrome in a murine high-fat diet model.

Immunology

Larissa M S Martins, Malena M Perez, Camila A Pereira, Frederico R C Costa, Murilo S Dias, Rita C Tostes, Simone G Ramos, Marcel R de Zoete, Bernhard Ryffel, João S Silva, Daniela Carlos

Affiliations

  1. Departments of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
  2. Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
  3. Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
  4. Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands.
  5. Molecular Immunology, University of Orleans and CNRS, INEM, UMR6218, Orleans, France.
  6. IDM, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.

PMID: 29722014 PMCID: PMC6050211 DOI: 10.1111/imm.12946

Abstract

We addressed the role of interleukin-23 (IL-23) in driving the intestinal T helper type 17 (Th17) response during obesity and metabolic syndrome progression induced by a high-fat diet (HFD). Diet-induced obese and lean mice received HFD or control diet (CTD), respectively, for 20 weeks. The nutritional, metabolic and immune parameters were examined at weeks 9 and 20. Gene and protein IL-23p19 and IL-23 receptor expression was increased in the ileum of obese wild-type mice (WT) fed the HFD for 9 weeks. Mice lacking IL-23 and fed the HFD exhibited greater weight gain, higher fat accumulation, adipocyte hypertrophy and hepatic steatosis. Notably, these mice had more glucose intolerance, insulin resistance and associated metabolic alterations, such as hyperinsulinaemia and hyperlipidaemia. IL-23 deficiency also significantly reduced protein levels of IL-17, CCL20 and neutrophil elastase in the ileum and reduced Th17 cell expansion in the mesenteric lymph nodes of the HFD mice. Of importance, IL-23-deficient mice exhibited increased gut permeability and blood bacterial translocation compared with WT mice fed HFD. Finally, metagenomics analysis of gut microbiota revealed a dramatic outgrowth of Bacteroidetes over Firmicutes phylum with the prevalence of Bacteroides genera in the faeces of IL-23-deficient mice after HFD. In summary, IL-23 appears to maintain the Th17 response and neutrophil migration into the intestinal mucosa, minimizing the gut dysbiosis and protecting against obesity and metabolic disease development in mice.

© 2018 John Wiley & Sons Ltd.

Keywords: gut microbiota; inflammation; interleukin-17-producing T helper lymphocytes; interleulin-23; metabolic disease; obesity

References

  1. Genome Biol. 2011 Jun 24;12(6):R60 - PubMed
  2. Nat Immunol. 2012 Oct;13(10):947-53 - PubMed
  3. Br J Nutr. 2010 Jul;104(1):83-92 - PubMed
  4. Cell. 2012 Mar 16;148(6):1160-71 - PubMed
  5. Hepatology. 2003 Apr;37(4):917-23 - PubMed
  6. Nat Med. 2014 Dec;20(12):1417-26 - PubMed
  7. Immunity. 2012 Jul 27;37(1):158-70 - PubMed
  8. Immunology. 2014 Aug;142(4):517-25 - PubMed
  9. Clin Chim Acta. 2006 Jun;368(1-2):1-19 - PubMed
  10. Diabetes. 2010 Dec;59(12):3049-57 - PubMed
  11. Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11070-5 - PubMed
  12. Gut. 2009 Aug;58(8):1091-103 - PubMed
  13. Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):13942-7 - PubMed
  14. J Exp Med. 2016 Jun 27;213(7):1223-39 - PubMed
  15. Immunol Rev. 2008 Dec;226:112-31 - PubMed
  16. Nat Rev Immunol. 2011 Feb;11(2):98-107 - PubMed
  17. Br Med Bull. 1997;53(2):307-21 - PubMed
  18. Science. 2006 Jun 2;312(5778):1355-9 - PubMed
  19. Gac Med Mex. 2012 Jul-Aug;148(4):381-9 - PubMed
  20. Nat Immunol. 2014 May;15(5):423-30 - PubMed
  21. Cell. 2009 Oct 30;139(3):485-98 - PubMed
  22. PLoS One. 2014 Mar 18;9(3):e92450 - PubMed
  23. Obesity (Silver Spring). 2012 Nov;20(11):2257-61 - PubMed
  24. Cell. 2014 Aug 28;158(5):1000-1010 - PubMed
  25. Proc Natl Acad Sci U S A. 2013 May 28;110(22):9066-71 - PubMed
  26. Gut Microbes. 2012 Jul-Aug;3(4):279-88 - PubMed
  27. Cell. 2013 Feb 14;152(4):673-84 - PubMed
  28. Cell Host Microbe. 2013 Sep 11;14(3):318-28 - PubMed
  29. Cell Host Microbe. 2012 Oct 18;12(4):445-57 - PubMed
  30. Nature. 2006 Dec 21;444(7122):1022-3 - PubMed
  31. Sci Transl Med. 2014 Jan 22;6(220):220ra11 - PubMed
  32. Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):637-44 - PubMed
  33. Blood. 2016 May 19;127(20):2460-71 - PubMed
  34. Free Radic Biol Med. 2011 Sep 1;51(5):993-9 - PubMed
  35. Nat Immunol. 2009 Mar;10(3):236-8 - PubMed
  36. Eur J Immunol. 2015 Oct;45(10):2873-85 - PubMed
  37. Gastroenterology. 2017 Jun;152(8):1998-2010 - PubMed
  38. J Immunol. 2001 Nov 15;167(10):6015-20 - PubMed
  39. Immunity. 2009 Sep 18;31(3):502-12 - PubMed
  40. Cell Metab. 2013 Apr 2;17(4):534-48 - PubMed
  41. J Mol Med (Berl). 2012 Feb;90(2):175-86 - PubMed
  42. Cell. 2012 Mar 16;148(6):1258-70 - PubMed
  43. Immunology. 2014 Jul;142(3):337-46 - PubMed
  44. Cell Host Microbe. 2008 Oct 16;4(4):337-49 - PubMed
  45. Trends Mol Med. 2013 Aug;19(8):487-500 - PubMed
  46. Eur J Immunol. 2009 Sep;39(9):2629-35 - PubMed
  47. Baillieres Clin Endocrinol Metab. 1994 Jul;8(3):661-88 - PubMed
  48. JAMA. 2002 Oct 9;288(14):1723-7 - PubMed
  49. Annu Rev Immunol. 2007;25:821-52 - PubMed
  50. Diabetes. 2007 Jul;56(7):1761-72 - PubMed
  51. Immunology. 2016 Dec;149(4):353-361 - PubMed
  52. BMC Immunol. 2017 Jun 24;18(1):33 - PubMed
  53. Diabetes. 2015 Jul;64(7):2477-88 - PubMed
  54. Cell. 2012 Mar 2;148(5):852-71 - PubMed
  55. Immunol Lett. 2011 Jul;138(1):4-6 - PubMed

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