title: Innate immunity and the pathogenesis of type 1 diabetes.
abstract: Type 1 diabetes mellitus is an autoimmune disease caused by the immune-mediated destruction of insulin-producing pancreatic beta cells occurring in genetically predisposed individuals, with consequent hyperglycemia and serious chronic complications. Studies in man and in experimental animal models have shown that both innate and adaptive immune responses participate to disease pathogenesis, possibly reflecting the multifactorial pathogenetic nature of this autoimmune disorder, with the likely involvement of environmental factors occurring at least in a subset of individuals. As a consequence, components of both innate and adaptive immune response should be considered as potential targets of therapeutic strategies for disease prevention and cure. Here we review the contribution of innate immune response to type 1 diabetes, with a particular emphasis to Toll-like receptors (TLR) and NK cells.
authors.affiliation: Diabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy.
authors.forename: Fabio Arturo
authors.initials: FA
authors.lastname: Grieco
authors.forename: Francesco
authors.initials: F
authors.lastname: Vendrame
authors.forename: Isabella
authors.initials: I
authors.lastname: Spagnuolo
authors.forename: Francesco
authors.initials: F
authors.lastname: Dotta
mesh_terms: D056704:Adaptive Immunity; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007113:Immunity, Innate; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D051193:Toll-Like Receptors
references.citation: Diabetes. 1992 Aug;41(8):1016-21
references.pmid: 1628761
references.citation: Nat Immunol. 2002 Sep;3(9):807-13
references.pmid: 12205470
references.citation: J Immunol. 1999 Apr 1;162(7):3749-52
references.pmid: 10201887
references.citation: Curr Opin Immunol. 2009 Dec;21(6):634-40
references.pmid: 19892538
references.citation: Diabetologia. 1993 Jul;36(7):596-601
references.pmid: 7689498
references.citation: Diabetes. 2008 Nov;57(11):3090-8
references.pmid: 18650365
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5115-20
references.pmid: 17360338
references.citation: J Exp Med. 2005 Jan 3;201(1):19-25
references.pmid: 15630134
references.citation: Endocrinology. 2002 Apr;143(4):1225-34
references.pmid: 11897677
references.citation: Diabetologia. 2009 Aug;52(8):1665-8
references.pmid: 19455302
references.citation: Diabetes. 2003 Oct;52(10):2639-42
references.pmid: 14514651
references.citation: Immunity. 2007 Aug;27(2):321-33
references.pmid: 17707128
references.citation: Int J Biochem Cell Biol. 2006;38(5-6):721-5
references.pmid: 16226050
references.citation: Blood. 2009 Feb 12;113(7):1399-407
references.pmid: 18757776
references.citation: Diabetes. 1990 Jul;39(7):836-43
references.pmid: 2191887
references.citation: Diabetologia. 1987 Dec;30(12):907-11
references.pmid: 3436487
references.citation: J Immunol. 2001 Aug 1;167(3):1179-87
references.pmid: 11466332
references.citation: Diabetes. 1983 Mar;32(3):247-53
references.pmid: 6298042
references.citation: J Immunol. 1986 Sep 15;137(6):1860-6
references.pmid: 3745917
references.citation: Nat Med. 2005 Oct;11(10):1059-65
references.pmid: 16155578
references.citation: J Immunol. 2004 Mar 1;172(5):3173-80
references.pmid: 14978124
references.citation: Nat Rev Immunol. 2003 Dec;3(12):984-93
references.pmid: 14647480
references.citation: Autoimmunity. 2007 Nov;40(7):540-5
references.pmid: 17966045
references.citation: J Immunol. 2004 Aug 15;173(4):2280-7
references.pmid: 15294940
references.citation: Diabetes. 1992 Apr;41(4):515-20
references.pmid: 1535056
references.citation: Nature. 2000 Dec 7;408(6813):740-5
references.pmid: 11130078
references.citation: J Clin Invest. 1986 Mar;77(3):916-24
references.pmid: 3512604
references.citation: Clin Dev Immunol. 2006 Jun-Dec;13(2-4):101-7
references.pmid: 17162353
references.citation: Biochem Biophys Res Commun. 2009 Oct 30;388(4):621-5
references.pmid: 19686699
references.citation: Nat Immunol. 2001 Aug;2(8):675-80
references.pmid: 11477402
references.citation: Clin Exp Immunol. 2003 Aug;133(2):208-18
references.pmid: 12869026
references.citation: Science. 2004 Mar 5;303(5663):1526-9
references.pmid: 14976262
references.citation: J Biol Chem. 2005 Oct 7;280(40):33984-91
references.pmid: 16027122
references.citation: J Clin Immunol. 1986 Sep;6(5):363-72
references.pmid: 2429979
references.citation: Cytokine. 2009 Jul;47(1):6-10
references.pmid: 19447045
references.citation: J Immunol. 2010 Mar 1;184(5):2272-80
references.pmid: 20130214
references.citation: Nat Rev Immunol. 2003 Oct;3(10):781-90
references.pmid: 14523385
references.citation: Front Biosci. 2008 May 01;13:6443-54
references.pmid: 18508671
references.citation: Diabetes. 1993 Mar;42(3):390-7
references.pmid: 8432409
references.citation: J Immunol. 2004 May 1;172(9):5356-62
references.pmid: 15100275
references.citation: Nat Rev Immunol. 2005 May;5(5):363-74
references.pmid: 15841099
references.citation: Diabetologia. 1984 Jul;27 Suppl:102-5
references.pmid: 6237011
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2992-7
references.pmid: 15710891
references.citation: Biochem J. 2009 Apr 28;420(1):1-16
references.pmid: 19382893
references.citation: Br Med J (Clin Res Ed). 1986 Jul 26;293(6541):244
references.pmid: 3089475
references.citation: J Autoimmun. 1989 Dec;2(6):759-76
references.pmid: 2533502
references.citation: Proc Natl Acad Sci U S A. 2004 May 25;101(21):8102-7
references.pmid: 15141080
references.citation: Diabetes. 2007 Jan;56(1):177-85
references.pmid: 17192480
references.citation: Nature. 2008 Oct 23;455(7216):1109-13
references.pmid: 18806780
references.citation: Annu Rev Immunol. 2000;18:861-926
references.pmid: 10837078
references.citation: Blood. 2008 Aug 1;112(3):461-9
references.pmid: 18650461
references.citation: J Clin Endocrinol Metab. 2008 Feb;93(2):578-83
references.pmid: 18029454
references.citation: Annu Rev Immunol. 2002;20:197-216
references.pmid: 11861602
references.citation: Nature. 2001 Oct 18;413(6857):732-8
references.pmid: 11607032
references.citation: Nature. 2001 Apr 26;410(6832):1099-103
references.pmid: 11323673
references.citation: Nat Immunol. 2004 Oct;5(10):987-95
references.pmid: 15454922
references.citation: Immunol Rev. 2000 Feb;173:89-97
references.pmid: 10719670
references.citation: Nat Rev Endocrinol. 2009 Apr;5(4):219-26
references.pmid: 19352320
references.citation: Eur J Immunol. 2008 Nov;38(11):2961-3
references.pmid: 18979518
references.citation: J Immunol. 2007 Feb 15;178(4):2141-7
references.pmid: 17277118
references.citation: Nat Immunol. 2002 Jun;3(6):499
references.pmid: 12032557
references.citation: Immunol Rev. 2008 Aug;224:70-84
references.pmid: 18759921
references.citation: Nat Immunol. 2004 Dec;5(12):1260-5
references.pmid: 15531883
references.citation: Diabetologia. 1986 Jun;29(6):352-7
references.pmid: 3527835
references.citation: J Immunol. 2008 Nov 15;181(10):7073-80
references.pmid: 18981127
references.citation: Clin Exp Immunol. 2010 Mar;159(3):338-43
references.pmid: 20059481
references.citation: Blood. 2003 Apr 15;101(8):3052-7
references.pmid: 12480696
references.citation: Int Immunol. 2009 Apr;21(4):317-37
references.pmid: 19246554
references.citation: Cell. 2006 Feb 24;124(4):783-801
references.pmid: 16497588
references.citation: J Immunol. 1999 Jul 1;163(1):57-61
references.pmid: 10384099
references.citation: Immunity. 2003 Jan;18(1):41-51
references.pmid: 12530974
references.citation: Tissue Antigens. 2007 Apr;69 Suppl 1:101-5
references.pmid: 17445178
references.citation: Diabet Med. 2006 Feb;23(2):156-63
references.pmid: 16433713
references.citation: Nat Immunol. 2010 Feb;11(2):121-8
references.pmid: 20023661
references.citation: Eur J Immunol. 2008 Nov;38(11):2942-5
references.pmid: 18979513
references.citation: Diabetes. 2001 Feb;50(2):283-90
references.pmid: 11272138
references.citation: Diabetes Res. 1991 Apr;16(4):171-5
references.pmid: 1802483
references.citation: Ann N Y Acad Sci. 2004 Dec;1037:161-9
references.pmid: 15699512
references.citation: Diabetes Res. 1991 May;17(1):37-41
references.pmid: 1823558
references.citation: Clin Exp Immunol. 2009 Feb;155(2):173-81
references.pmid: 19128359
references.citation: Diabetes. 2008 May;57(5):1236-45
references.pmid: 18223009
references.citation: Nat Immunol. 2002 Feb;3(2):196-200
references.pmid: 11812998
references.citation: Int Immunol. 2004 Jan;16(1):1-11
references.pmid: 14688055
references.citation: Nat Rev Endocrinol. 2010 Mar;6(3):158-66
references.pmid: 20173777
references.citation: J Immunol. 2004 Feb 1;172(3):1455-62
references.pmid: 14734722
references.citation: Nature. 2007 Oct 18;449(7164):819-26
references.pmid: 17943118
references.citation: Immunity. 1999 Oct;11(4):443-51
references.pmid: 10549626
references.citation: Annu Rev Immunol. 2001;19:197-223
references.pmid: 11244035
references.citation: J Autoimmun. 1995 Dec;8(6):843-57
references.pmid: 8824710
references.citation: Cell Death Differ. 2006 May;13(5):816-25
references.pmid: 16410796
references.citation: Diabetes Res Clin Pract. 1994 Feb;23(1):37-42
references.pmid: 7516851
references.citation: Immunobiology. 1990 Jun;180(4-5):431-40
references.pmid: 2204602
references.citation: Nat Immunol. 2008 May;9(5):503-10
references.pmid: 18425107
references.citation: J Immunol. 2004 Jan 15;172(2):937-42
references.pmid: 14707066
references.citation: Annu Rev Immunol. 2004;22:405-29
references.pmid: 15032583
references.citation: Eur J Immunol. 2008 Jan;38(1):82-9
references.pmid: 18085661
references.citation: Nat Med. 2007 May;13(5):543-51
references.pmid: 17479100
references.citation: Nat Immunol. 2002 Apr;3(4):373-82
references.pmid: 11919579