Reduced expression of central innate defense molecules in pancreatic biopsies from subjects with Type 1 diabetes.
Biopsy
Defensins
Etiopathology
Innate immunity
Pancreas
Type 1 diabetes
Journal
Acta diabetologica
ISSN: 1432-5233
Titre abrégé: Acta Diabetol
Pays: Germany
ID NLM: 9200299
Informations de publication
Date de publication:
08 May 2024
08 May 2024
Historique:
received:
06
09
2023
accepted:
06
04
2024
medline:
8
5
2024
pubmed:
8
5
2024
entrez:
8
5
2024
Statut:
aheadofprint
Résumé
Defensins play a crucial role in the innate immune system's first defense against microbial threats. However, little is known about the defensin system in the pancreas, especially in relation to Type 1 diabetes. We explore the expression of defensins in different disease stages of Type 1 diabetes and correlated obtained findings to the degree of inflammation, providing new insights into the disease and the innate immune system. Pancreases from non-diabetic human organ donors of different age groups and donors with Type 1 diabetes with different disease duration were examined. Sections from head, body and tail of the pancreas were stained for eight different defensins and for immune cells; CD3+, CD45+, CD68+ and NES+ (granulocytes). In non-diabetic adult controls the level of expression for defensins Beta-1,Alpha-1, Cathelicidin and REG3A correlated with the level of inflammation. In contrast, individuals with Type 1 diabetes exhibit a reduction or absence of several central defensins regardless of the level of inflammation in their pancreas. The expression of Cathelicidin is present in neutrophils and macrophages but not in T-cells in subjects with Type 1 diabetes. Obtained findings suggest a pancreatic dysfunction in the innate immune system and the bridging to the adaptive system in Type 1 diabetes. Further studies on the role of the local innate immune system in Type 1 diabetes is needed.
Identifiants
pubmed: 38717484
doi: 10.1007/s00592-024-02286-1
pii: 10.1007/s00592-024-02286-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
Références
Lehrer RI, Lu W (2012) α-Defensins in human innate immunity. Immunol Rev 245(1):84–112
doi: 10.1111/j.1600-065X.2011.01082.x
pubmed: 22168415
Pazgier M, Li X, Lu W, Lubkowski J (2007) Human defensins: synthesis and structural properties. Curr Pharm Des 13(30):3096–3118
doi: 10.2174/138161207782110381
pubmed: 17979752
Zhao L, Lu W (2014) Defensins in innate immunity. Curr Opin Hematol 21(1):37–42
doi: 10.1097/MOH.0000000000000005
pubmed: 24275690
Nakamura K, Sakurigon N, Takakuwa A, Ayabe T (2016) Paneth cell α-defensins and enteric microbiota in health and disease. Biosci Microbiota Food Health 35(2):57–67
doi: 10.12938/bmfh.2015-019
pubmed: 27200259
Xu D, Lu W (2020) Defensins: a double-edged sword in host immunity. Front Immunol 11:764
doi: 10.3389/fimmu.2020.00764
pubmed: 32457744
pmcid: 7224315
Zhao C, Wang I, Lehrer RI (1996) Widespread expression of beta-defensin hBD-1 in human secretory glands and epithelial cells. FEBS Lett 396(2–3):319–322
doi: 10.1016/0014-5793(96)01123-4
pubmed: 8915011
Koeninger L, Armbruster NS, Brinch KS et al (2020) Human β-defensin 2 mediated immune modulation as treatment for experimental colitis. Front Immunol 31(11):93
doi: 10.3389/fimmu.2020.00093
Yang D, Chertov O, Bykovskaia SN et al (1999) β-Defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286(5439):525–528
doi: 10.1126/science.286.5439.525
pubmed: 10521347
Joly S, Maze C, McCray PB, Guthmiller JM (2004) Human β-defensins 2 and 3 demonstrate strain-selective activity against oral microorganisms. J Clin Microbiol 42(3):1024–1029
doi: 10.1128/JCM.42.3.1024-1029.2004
pubmed: 15004048
pmcid: 356847
Kanda N, Kamata M, Tada Y, Ishikawa T, Sato S, Watanabe S (2011) Human β-defensin-2 enhances IFN-γ and IL-10 production and suppresses IL-17 production in T cells. J Leukoc Biol 89(6):935–944
doi: 10.1189/jlb.0111004
pubmed: 21367976
Machado LR, Ottolini B (2015) An evolutionary history of defensins: a role for copy number variation in maximizing host innate and adaptive immune responses. Front Immunol 18(6):115
Stenwall A, Ingvast S, Skog O, Korsgren O (2019) Characterization of host defense molecules in the human pancreas. Islets 11(4):89–101
doi: 10.1080/19382014.2019.1585165
pubmed: 31242128
pmcid: 6682263
Schnapp D, Reid CJ, Harris A (1998) Localization of expression of human beta defensin-1 in the pancreas and kidney. J Pathol 186(1):99–103
doi: 10.1002/(SICI)1096-9896(199809)186:1<99::AID-PATH133>3.0.CO;2-#
pubmed: 9875146
Gepts W (1965) Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 14(10):619–633
doi: 10.2337/diab.14.10.619
pubmed: 5318831
Gaglia JL, Harisinghani M, Aganj I et al (2015) Noninvasive mapping of pancreatic inflammation in recent-onset type-1 diabetes patients. Proc Natl Acad Sci 112(7):2139–2144
doi: 10.1073/pnas.1424993112
pubmed: 25650428
pmcid: 4343112
Coppieters KT, Dotta F, Amirian N et al (2012) Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. J Exp Med 209(1):51–60
doi: 10.1084/jem.20111187
pubmed: 22213807
pmcid: 3260877
Korsgren S, Molin Y, Salmela K, Lundgren T, Melhus Å, Korsgren O (2012) On the etiology of type 1 diabetes: a new animal model signifying a decisive role for bacteria eliciting an adverse innate immunity response. Am J Pathol 181(5):1735–1748
doi: 10.1016/j.ajpath.2012.07.022
pubmed: 22944599
pmcid: 3483807
Cerqueiro Bybrant M, Grahnquist L, Örtqvist E et al (2018) Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: a Swedish nationwide prospective population-based cohort study. Autoimmunity 51(5):221–227
doi: 10.1080/08916934.2018.1494160
pubmed: 30444426
Angie T, Sofie I, Åsa M, Oskar S, Olle K (2022) A decisive bridge between innate immunity and the pathognomonic morphological characteristics of type 1 diabetes demonstrated by instillation of heat-inactivated bacteria in the pancreatic duct of rats. Acta Diabetol 59(8):1011–1018
doi: 10.1007/s00592-022-01881-4
pubmed: 35461380
pmcid: 9242896
de Goffau MC, Luopajärvi K, Knip M et al (2013) Fecal microbiota composition differs between children with β-cell autoimmunity and those without. Diabetes 62(4):1238–1244
doi: 10.2337/db12-0526
pubmed: 23274889
pmcid: 3609581
Bosi E, Molteni L, Radaelli MG et al (2006) Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia 49(12):2824–2827
doi: 10.1007/s00125-006-0465-3
pubmed: 17028899
Krogvold L, Edwin B, Buanes T et al (2014) Pancreatic biopsy by minimal tail resection in live adult patients at the onset of type 1 diabetes: experiences from the DiViD study. Diabetologia 57(4):841–843
doi: 10.1007/s00125-013-3155-y
pubmed: 24429579
Barnea M, Madar Z, Froy O (2008) Glucose and insulin are needed for optimal defensin expression in human cell lines. Biochem Biophys Res Commun 367(2):452–456
doi: 10.1016/j.bbrc.2007.12.158
pubmed: 18178160
Diamond G, Kaiser V, Rhodes J, Russell JP, Bevins CL (2000) Transcriptional regulation of β-defensin gene expression in tracheal epithelial cells. Infect Immun 68(1):113–119
doi: 10.1128/IAI.68.1.113-119.2000
pubmed: 10603376
pmcid: 97109
Page RA, Malik AN (2003) Elevated levels of beta defensin-1 mRNA in diabetic kidneys of GK rats. Biochem Biophys Res Commun 310(2):513–521
doi: 10.1016/j.bbrc.2003.09.034
pubmed: 14521940
Wehkamp J, Salzman NH, Porter E et al (2005) Reduced Paneth cell α-defensins in ileal Crohn’s disease. Proc Natl Acad Sci U S A 102(50):18129–18134
doi: 10.1073/pnas.0505256102
pubmed: 16330776
pmcid: 1306791
Kościuczuk EM, Lisowski P, Jarczak J et al (2012) Cathelicidins: family of antimicrobial peptides. A review. Mol Biol Rep 39(12):10957–10970
doi: 10.1007/s11033-012-1997-x
pubmed: 23065264
pmcid: 3487008
Dürr UHN, Sudheendra US, Ramamoorthy A (2006) LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta (BBA) Biomembr 1758(9):1408–1425
doi: 10.1016/j.bbamem.2006.03.030
Acen EL, Biraro IA, Worodria W et al (2021) Impact of vitamin D status and cathelicidin antimicrobial peptide on adults with active pulmonary TB globally: a systematic review and meta-analysis. PLoS ONE 16(6):e0252762
doi: 10.1371/journal.pone.0252762
pubmed: 34115790
pmcid: 8195352
Mathieu C, Badenhoop K (2005) Vitamin D and type 1 diabetes mellitus: state of the art. Trends Endocrinol Metab 16(6):261–266
doi: 10.1016/j.tem.2005.06.004
pubmed: 15996876
Hou Y, Song A, Jin Y, Xia Q, Song G, Xing X (2021) A dose–response meta-analysis between serum concentration of 25-hydroxy vitamin D and risk of type 1 diabetes mellitus. Eur J Clin Nutr 75(7):1010–1023
doi: 10.1038/s41430-020-00813-1
pubmed: 33235321
Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE (2007) Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 179(3):1634–1647
doi: 10.4049/jimmunol.179.3.1634
pubmed: 17641030
Savastio S, Cadario F, Genoni G et al (2016) Vitamin D deficiency and glycemic status in children and adolescents with type 1 diabetes mellitus. PLoS ONE 11(9):e0162554
doi: 10.1371/journal.pone.0162554
pubmed: 27607348
pmcid: 5015862
Guo J, Fu W (2020) Immune regulation of islet homeostasis and adaptation. J Mol Cell Biol 12(10):764–774
doi: 10.1093/jmcb/mjaa009
pubmed: 32236479
pmcid: 7816675
Cui W, De Jesus K, Zhao H et al (2009) Overexpression of Reg3α increases cell growth and the levels of cyclin D1 and CDK4 in insulinoma cells. Growth Factors 27(3):195–202
doi: 10.1080/08977190902863548
pubmed: 19343564
Ding Y, Xu Y, Shuai X et al (2014) Reg3α overexpression protects pancreatic β cells from cytokine-induced damage and improves islet transplant outcome. Mol Med 20(1):548–558
doi: 10.2119/molmed.2014.00104
Yu L, Li L, Liu J et al (2022) Recombinant Reg3α prevents Islet β-cell apoptosis and promotes β-cell regeneration. Int J Mol Sci 23(18):10584
doi: 10.3390/ijms231810584
pubmed: 36142497
pmcid: 9504149