دورية أكاديمية
أعرض في EDS

The DNA Sensor AIM2 Protects against Streptozotocin-Induced Type 1 Diabetes by Regulating Intestinal Homeostasis via the IL-18 Pathway.

التفاصيل البيبلوغرافية
العنوان: The DNA Sensor AIM2 Protects against Streptozotocin-Induced Type 1 Diabetes by Regulating Intestinal Homeostasis via the IL-18 Pathway.
المؤلفون: Leite JA; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, USP-Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo 14049-900, Brazil.; Institute of Biomedical Science IV-University of São Paulo (USP), São Paulo, São Paulo 14049-900, Brazil., Pessenda G; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, USP-Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo 14049-900, Brazil., Guerra-Gomes IC; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, USP-Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo 14049-900, Brazil., de Santana AKM; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, USP-Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo 14049-900, Brazil., André Pereira C; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo 14049-900, Brazil., Ribeiro Campos Costa F; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, USP-Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo 14049-900, Brazil., Ramos SG; Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo 14049-900, Brazil., Simões Zamboni D; Department of Molecular and Cell Biology, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo 14049-900, Brazil., Caetano Faria AM; Department of Biochemistry and Immunology, Institute of Biological Science-Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais 31270-901, Brazil., Candido de Almeida D; Department of Immunology-Federal University of São Paulo (UNIFESP), São Paulo, São Paulo 04021-001, Brazil., Olsen Saraiva Câmara N; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, USP-Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo 14049-900, Brazil.; Institute of Biomedical Science IV-University of São Paulo (USP), São Paulo, São Paulo 14049-900, Brazil.; Department of Immunology-Federal University of São Paulo (UNIFESP), São Paulo, São Paulo 04021-001, Brazil., Tostes RC; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo 14049-900, Brazil., Santana Silva J; Fiocruz- Bi-Institutional Translational Medicine Platform, Ribeirão Preto, São Paulo 14049-900, Brazil., Carlos D; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, USP-Avenida Bandeirantes 3900, Monte Alegre, Ribeirão Preto, São Paulo 14049-900, Brazil.
المصدر: Cells [Cells] 2020 Apr 14; Vol. 9 (4). Date of Electronic Publication: 2020 Apr 14.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: DNA-Binding Proteins/*therapeutic use , Diabetes Mellitus, Experimental/*genetics , Immunity, Innate/*genetics, Animals ; Homeostasis ; Humans ; Interleukin-18/metabolism ; Male ; Mice ; Mice, Inbred C57BL
مستخلص: Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL/6 mice lacking AIM2 (AIM2 -/- ) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL/6 mice. The AIM2 -/- mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2 -/- mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIIIγ production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing β cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model.
References: Genome Med. 2016 Apr 21;8(1):43. (PMID: 27102666)
Curr Gastroenterol Rep. 1999 Oct;1(5):410-6. (PMID: 10980980)
Diabet Med. 2005 Apr;22(4):359-70. (PMID: 15787657)
BMJ. 2001 Apr 14;322(7291):889-92. (PMID: 11302899)
Gut. 2006 Oct;55(10):1512-20. (PMID: 16966705)
Lancet. 2016 Jun 4;387(10035):2340-2348. (PMID: 27302273)
Microbiome. 2018 Feb 17;6(1):35. (PMID: 29454391)
BMC Med. 2013 Feb 21;11:46. (PMID: 23433344)
Pharmacol Res. 2017 May;119:219-226. (PMID: 28188825)
Proc Natl Acad Sci U S A. 1980 Oct;77(10):6129-33. (PMID: 6449703)
BMC Gastroenterol. 2011 Oct 06;11:109. (PMID: 21977944)
Gastroenterology. 2009 Aug;137(2):732-4. (PMID: 19567237)
Diabetologia. 2006 Sep;49(9):2105-8. (PMID: 16816951)
Front Immunol. 2017 Feb 27;8:164. (PMID: 28289409)
Exp Biol Med (Maywood). 2001 Nov;226(10):898-905. (PMID: 11682695)
J Interferon Cytokine Res. 2013 Apr;33(4):162-70. (PMID: 23570382)
Diabetologia. 2003 Mar;46(3):305-21. (PMID: 12687328)
Rev Diabet Stud. 2012 Winter;9(4):251-9. (PMID: 23804264)
J Autoimmun. 2018 Dec;95:47-57. (PMID: 30340822)
Cell Rep. 2015 Dec 1;13(9):1922-36. (PMID: 26655906)
Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):9973-7. (PMID: 26216961)
J Autoimmun. 2018 Sep;93:57-65. (PMID: 29960834)
Exp Clin Endocrinol Diabetes. 2017 Sep;125(8):563-570. (PMID: 28750427)
Annu Rev Nutr. 1995;15:35-55. (PMID: 8527224)
Diabetologia. 2012 Nov;55(11):2868-77. (PMID: 22875196)
Diabetologia. 2006 Dec;49(12):2824-7. (PMID: 17028899)
Nat Immunol. 2010 May;11(5):395-402. (PMID: 20351692)
Science. 2018 Mar 9;359(6380):1156-1161. (PMID: 29590047)
J Immunol. 2003 Mar 15;170(6):3059-64. (PMID: 12626561)
JPEN J Parenter Enteral Nutr. 2011 Sep;35(5 Suppl):14S-20S. (PMID: 21807932)
Nature. 2001 Dec 13;414(6865):792-8. (PMID: 11742411)
J Leukoc Biol. 2019 Sep;106(3):513-529. (PMID: 31313381)
Cell Mol Immunol. 2017 Jan;14(1):127-142. (PMID: 27524110)
Nature. 2009 Mar 26;458(7237):514-8. (PMID: 19158675)
J Immunol. 2010 May 15;184(10):5645-53. (PMID: 20393135)
Science. 2018 Jan 5;359(6371):104-108. (PMID: 29302014)
Gut. 2004 Dec;53(12):1724-5. (PMID: 15542502)
Rev Esp Enferm Dig. 2015 Nov;107(11):672-6. (PMID: 26541656)
Immunobiology. 2013 Mar;218(3):338-52. (PMID: 22704522)
N Engl J Med. 2002 Sep 19;347(12):911-20. (PMID: 12239261)
Diabetes. 2006 May;55(5):1443-9. (PMID: 16644703)
Sci Transl Med. 2011 May 11;3(82):82ra38. (PMID: 21562230)
Eur J Immunol. 2016 Feb;46(2):269-80. (PMID: 26626159)
Immunity. 2012 Aug 24;37(2):326-38. (PMID: 22902233)
J Clin Immunol. 2013 Jul;33(5):925-37. (PMID: 23479181)
Pediatr Allergy Immunol. 2013 Sep;24(6):589-95. (PMID: 23909601)
Diabetologia. 2014 Aug;57(8):1569-77. (PMID: 24930037)
J Exp Med. 2016 Jun 27;213(7):1223-39. (PMID: 27325889)
J Clin Endocrinol Metab. 2007 Sep;92(9):3705-11. (PMID: 17595242)
Curr Opin Gastroenterol. 2008 Nov;24(6):701-6. (PMID: 19122519)
J Med Microbiol. 2014 Feb;63(Pt 2):293-308. (PMID: 24255136)
PLoS One. 2010 Dec 17;5(12):e15263. (PMID: 21179419)
Autoimmunity. 2010 Dec;43(8):583-9. (PMID: 20370570)
Diabetes. 1994 Aug;43(8):992-8. (PMID: 8039607)
PLoS One. 2012;7(3):e34233. (PMID: 22457829)
فهرسة مساهمة: Keywords: AIM2 receptor; Innate immunity; Type 1 diabetes
المشرفين على المادة: 0 (AIM2 protein, human)
0 (Aim2 protein, mouse)
0 (DNA-Binding Proteins)
0 (Interleukin-18)
تواريخ الأحداث: Date Created: 20200417 Date Completed: 20210315 Latest Revision: 20210315
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7227011
DOI: 10.3390/cells9040959
PMID: 32295112
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4409
DOI:10.3390/cells9040959