NOD2

NOD2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	5IRL, 5IRM, 5IRN
Identifikatori
Aliasi	NOD2
Vanjski ID-jevi	OMIM: 605956 MGI: 2429397 HomoloGene: 11156 GeneCards: NOD2
Lokacija gena (čovjek)
Hrom.	Hromosom 16 (čovjek)
Kraj	50,734,041 bp
Lokacija gena (miš)
Hrom.	Hromosom 8 (miš)
Kraj	89,415,102 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• Hsp90 protein binding; • nucleotide binding; • Hsp70 protein binding; • GO:0001948, GO:0016582 vezivanje za proteine; • peptidoglycan binding; • vezivanje enzima; • actin binding; • CARD domain binding; • ATP binding; • protein kinase binding; • muramyl dipeptide binding; • GO:0032403 protein-containing complex binding;
Ćelijska komponenta	• citoplazma; • citosol; • Vezikula; • membrana; • ćelijska membrana; • cell surface; • basolateral plasma membrane; • COP9 signalosome; • citoskelet; • Golđijev aparat; • mitohondrija; • GO:0009327 makromolekulani kompleks;
Biološki proces	• positive regulation of prostaglandin-endoperoxide synthase activity; • regulation of apoptotic process; • defense response; • detection of biotic stimulus; • cytokine production involved in immune response; • positive regulation of cytokine production involved in inflammatory response; • GO:0007243 intracellular signal transduction; • detection of muramyl dipeptide; • positive regulation of interleukin-10 production; • positive regulation of epithelial cell proliferation; • immune system process; • GO:1900490 positive regulation of oxidoreductase activity; • response to muramyl dipeptide; • positive regulation of prostaglandin-E synthase activity; • positive regulation of JNK cascade; • positive regulation of nitric-oxide synthase biosynthetic process; • positive regulation of NIK/NF-kappaB signaling; • positive regulation of phosphatidylinositol 3-kinase activity; • positive regulation of gamma-delta T cell activation; • cellular response to muramyl dipeptide; • JNK cascade; • negative regulation of macrophage apoptotic process; • positive regulation of dendritic cell antigen processing and presentation; • nucleotide-binding oligomerization domain containing 2 signaling pathway; • maintenance of gastrointestinal epithelium; • defense response to bacterium; • positive regulation of NF-kappaB transcription factor activity; • positive regulation of interleukin-8 production; • detection of bacterium; • positive regulation of interleukin-1 beta production; • regulation of inflammatory response; • positive regulation of interleukin-6 production; • protein complex oligomerization; • positive regulation of tumor necrosis factor production; • positive regulation of ERK1 and ERK2 cascade; • positive regulation of I-kappaB kinase/NF-kappaB signaling; • positive regulation of B cell activation; • positive regulation of interleukin-17 production; • positive regulation of type 2 immune response; • nucleotide-binding oligomerization domain containing signaling pathway; • positive regulation of stress-activated MAPK cascade; • positive regulation of Notch signaling pathway; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II; • GO:1904579 cellular response to organic cyclic compound; • positive regulation of cell population proliferation; • Urođeni imunski sistem; • response to nutrient; • positive regulation of dendritic cell cytokine production; • positive regulation of protein K63-linked ubiquitination; • cellular response to peptidoglycan; • positive regulation of MAP kinase activity; • interleukin-1-mediated signaling pathway; • cellular response to lipopolysaccharide;
	Izvori:Amigo / QuickGO
Ortolozi
	64127
	257632
	ENSG00000167207
	ENSMUSG00000055994
	Q9HC29
	Q80SY9
	NM_001293557; NM_022162; NM_001370466
	NM_145857
	NP_001280486; NP_071445; NP_001357395
	NP_665856
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Protein 2 sa nukleotid-vezujućim domenom oligomerizacije (NOD2), znan i kao protein 15 sa domenom regrotacije kaspaze (CARD15) ili protein 1 upalne bolesti crijeva (IBD1), jest protein koji je kod ljudi kodiran genom NOD2 sa p kraka hromosoma 16.^[5]^[6] NOD2 ima važnu ulogu u imunskom sistemu. Prepoznaje bakterijske molekule (peptidoglikane) i stimulira imunsku reakciju.^[7]

NOD2 je unutarćelijski receptor prepoznavanja uzorka, koji je po strukturi sličan rezistentnim proteinima biljaka i prepoznaje molekule koji sadrže specifičnu strukturu zvanu muramil-dipeptid (MDP) koja se nalazi u određenim bakterijama.^[8]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.040 aminokiselina, a molekulska težina 115.283 Da.^[9]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MGEEGGSASH	DEEERASVLL	GHSPGCEMCS	QEAFQAQRSQ	LVELLVSGSL
EGFESVLDWL	LSWEVLSWED	YEGFHLLGQP	LSHLARRLLD	TVWNKGTWAC
QKLIAAAQEA	QADSQSPKLH	GCWDPHSLHP	ARDLQSHRPA	IVRRLHSHVE
NMLDLAWERG	FVSQYECDEI	RLPIFTPSQR	ARRLLDLATV	KANGLAAFLL
QHVQELPVPL	ALPLEAATCK	KYMAKLRTTV	SAQSRFLSTY	DGAETLCLED
IYTENVLEVW	ADVGMAGPPQ	KSPATLGLEE	LFSTPGHLND	DADTVLVVGE
AGSGKSTLLQ	RLHLLWAAGQ	DFQEFLFVFP	FSCRQLQCMA	KPLSVRTLLF
EHCCWPDVGQ	EDIFQLLLDH	PDRVLLTFDG	FDEFKFRFTD	RERHCSPTDP
TSVQTLLFNL	LQGNLLKNAR	KVVTSRPAAV	SAFLRKYIRT	EFNLKGFSEQ
GIELYLRKRH	HEPGVADRLI	RLLQETSALH	GLCHLPVFSW	MVSKCHQELL
LQEGGSPKTT	TDMYLLILQH	FLLHATPPDS	ASQGLGPSLL	RGRLPTLLHL
GRLALWGLGM	CCYVFSAQQL	QAAQVSPDDI	SLGFLVRAKG	VVPGSTAPLE
FLHITFQCFF	AAFYLALSAD	VPPALLRHLF	NCGRPGNSPM	ARLLPTMCIQ
ASEGKDSSVA	ALLQKAEPHN	LQITAAFLAG	LLSREHWGLL	AECQTSEKAL
LRRQACARWC	LARSLRKHFH	SIPPAAPGEA	KSVHAMPGFI	WLIRSLYEMQ
EERLARKAAR	GLNVGHLKLT	FCSVGPTECA	ALAFVLQHLR	RPVALQLDYN
SVGDIGVEQL	LPCLGVCKAL	YLRDNNISDR	GICKLIECAL	HCEQLQKLAL
FNNKLTDGCA	HSMAKLLACR	QNFLALRLGN	NYITAAGAQV	LAEGLRGNTS
LQFLGFWGNR	VGDEGAQALA	EALGDHQSLR	WLSLVGNNIG	SVGAQALALM
LAKNVMLEEL	CLEENHLQDE	GVCSLAEGLK	KNSSLKILKL	SNNCITYLGA
EALLQALERN	DTILEVWLRG	NTFSLEEVDK	LGCRDTRLLL

Struktura

C-terminalni dio proteina sadrži ponavljanje bogato leucinom, domen za koji je poznato da ima ulogu u interakcijama protein-protein. Srednji dio proteina karakterizira NOD-ov domen uključen u samooligomerizaciju proteina. N-terminalni dio sadrži dva CARD domena za koje se zna da imaju ulogu u apoptozi i NF-κB putevima aktivacije.^[11]

Funkcija

Ovaj gen je član porodice NOD1/Apaf-1 (također poznate kao porodica NOD-liki receptori) i kodira protein sa dva domena regrutacije kaspaze ( CARD-a) i jedanaest ponavljanja bogatih leucinom (LRR). Protein se prvenstveno eksprimira u leukocitima periferne krvi. Ima ulogu u imunskom odgovoru, tako što prepoznaje bakterijske molekule koje posjeduju muramil-dipeptidni (MDP) dio i aktivira NF-κB protein.^[9]

Klinički značaj

Mutacije ovog gena su povezane sa Crohnovom bolešću,^[10] Blauovim sindromom, teškom plućnom sarkoidozom^[12] i bolešću transplanta protiv domaćina.^[13]

NOD2 gen je povezan sa upalnim bolestima kao što su upalna bolest crijeva/Crohnova bolest i Blauov sindrom.^[14]^[15]

Interakcije

Pokazalo se da NOD2 reaguje sa NLRC4.^[16]^[17]

Također se pokazalo da se NOD2 vezuje za MAVS, kao odgovor na tretman ssRNK ili virusne RNK i aktivira IFN odgovor. Ovo je prvi izvještaj da NOD2 djeluje kao receptor za prepoznavanje uzoraka za viruse.^[18]

Također pogledajte

Mifamurtid, NOD2 aktivator za liječenje osteosarkoma

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000167207 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000055994 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Gilberts EC, Greenstein AJ, Katsel P, Harpaz N, Greenstein RJ (Dec 1994). "Molecular evidence for two forms of Crohn disease". Proceedings of the National Academy of Sciences of the United States of America. 91 (26): 12721–4. Bibcode:1994PNAS...9112721G. doi:10.1073/pnas.91.26.12721. PMC 45511. PMID 7809109.
^ Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, Beaugerie L, Naom I, Dupas JL, Van Gossum A, Orholm M, Bonaiti-Pellie C, Weissenbach J, Mathew CG, Lennard-Jones JE, Cortot A, Colombel JF, Thomas G (Feb 1996). "Mapping of a susceptibility locus for Crohn's disease on chromosome 16". Nature. 379 (6568): 821–3. Bibcode:1996Natur.379..821H. doi:10.1038/379821a0. PMID 8587604. S2CID 4311407.
^ Mahla RS, Reddy MC, Prasad DV, Kumar H (septembar 2013). "Sweeten PAMPs: Role of Sugar Complexed PAMPs in Innate Immunity and Vaccine Biology". Frontiers in Immunology. 4: 248. doi:10.3389/fimmu.2013.00248. PMC 3759294. PMID 24032031.
^ Kufer TA, Banks DJ, Philpott DJ (Aug 2006). "Innate immune sensing of microbes by Nod proteins". Annals of the New York Academy of Sciences. 1072 (1): 19–27. Bibcode:2006NYASA1072...19K. doi:10.1196/annals.1326.020. PMID 17057187. S2CID 20217610.
^ ^a ^b "Entrez Gene: NOD2 nucleotide-binding oligomerization domain containing 2".
^ ^a ^b Nakagome S, Mano S, Kozlowski L, Bujnicki JM, Shibata H, Fukumaki Y, Kidd JR, Kidd KK, Kawamura S, Oota H (Jun 2012). "Crohn's disease risk alleles on the NOD2 locus have been maintained by natural selection on standing variation". Molecular Biology and Evolution. 29 (6): 1569–85. doi:10.1093/molbev/mss006. PMC 3697811. PMID 22319155.
^ Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G (Feb 2001). "Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB". The Journal of Biological Chemistry. 276 (7): 4812–8. doi:10.1074/jbc.M008072200. PMID 11087742.
^ Sato H, Williams HR, Spagnolo P, Abdallah A, Ahmad T, Orchard TR, Copley SJ, Desai SR, Wells AU, du Bois RM, Welsh KI (Feb 2010). "CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis". Eur Respir J. 35 (2): 324–30. doi:10.1183/09031936.00010209. PMID 19679608.
^ Zhao H, Jia M, Wang Z, Cheng Y, Luo Z, Chen Y, Xu X, Yang S, Tang Y (Jun 2015). "Association between NOD2 single nucleotide polymorphisms and Grade III-IV acute graft-versus-host disease: A meta-analysis". Hematology. 20 (5): 254–62. doi:10.1179/1607845414Y.0000000202. PMID 25248089. S2CID 206850232.
^ Radford-Smith G, Pandeya N (Nov 2006). "Associations between NOD2/CARD15 genotype and phenotype in Crohn's disease--Are we there yet?". World Journal of Gastroenterology. 12 (44): 7097–103. doi:10.3748/wjg.v12.i44.7097. PMC 4087769. PMID 17131470.
^ Kim TH, Payne U, Zhang X, Iwanaga Y, Davey MP, Rosenbaum JT, Inman RD (Jan 2007). "Altered host:pathogen interactions conferred by the Blau syndrome mutation of NOD2". Rheumatology International. 27 (3): 257–62. doi:10.1007/s00296-006-0250-0. PMID 17096091. S2CID 23739992.
^ Damiano JS, Oliveira V, Welsh K, Reed JC (Jul 2004). "Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses". The Biochemical Journal. 381 (Pt 1): 213–9. doi:10.1042/BJ20031506. PMC 1133779. PMID 15107016.
^ Damiano JS, Stehlik C, Pio F, Godzik A, Reed JC (Jul 2001). "CLAN, a novel human CED-4-like gene". Genomics. 75 (1–3): 77–83. doi:10.1006/geno.2001.6579. PMID 11472070.
^ Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, Bose S (Oct 2009). "Activation of innate immune antiviral responses by Nod2". Nature Immunology. 10 (10): 1073–80. doi:10.1038/ni.1782. PMC 2752345. PMID 19701189.

Dopunska literatura

Punchard NA (Oct 2001). "Overview: Nod2, cause of, or contributor to, Crohn's disease". Current Opinion in Investigational Drugs. 2 (10): 1378–81. PMID 11890351.
Satsangi J, Morecroft J, Shah NB, Nimmo E (Feb 2003). "Genetics of inflammatory bowel disease: scientific and clinical implications". Best Practice & Research. Clinical Gastroenterology. 17 (1): 3–18. doi:10.1053/bega.2002.0349. PMID 12617879.
Rosenbaum JT, Planck SR, Davey MP, Iwanaga Y, Kurz DE, Martin TM (Oct 2003). "With a mere nod, uveitis enters a new era". American Journal of Ophthalmology. 136 (4): 729–32. doi:10.1016/S0002-9394(03)00569-5. PMID 14516815.
Kurokawa T, Kikuchi T, Ohta K, Imai H, Yoshimura N (Oct 2003). "Ocular manifestations in Blau syndrome associated with a CARD15/Nod2 mutation". Ophthalmology. 110 (10): 2040–4. doi:10.1016/S0161-6420(03)00717-6. PMID 14522785.
Girardin SE, Hugot JP, Sansonetti PJ (Dec 2003). "Lessons from Nod2 studies: towards a link between Crohn's disease and bacterial sensing". Trends in Immunology. 24 (12): 652–8. doi:10.1016/j.it.2003.10.007. PMID 14644139.
Newman B, Siminovitch K (Dec 2003). "Inflammatory bowel disease: Crohn's disease and the success of NODern genetics". Clinical and Investigative Medicine. 26 (6): 303–14. PMID 14690304.
Oostenbrug LE, van Dullemen HM, te Meerman GJ, Jansen PL (2003). "IBD and genetics: new developments". Scandinavian Journal of Gastroenterology. Supplement. 38 (239): 63–8. doi:10.1080/00855920310002717. PMID 14743885.
Kambe N, Nishikomori R, Kanazawa N (Aug 2005). "The cytosolic pattern-recognition receptor Nod2 and inflammatory granulomatous disorders". Journal of Dermatological Science. 39 (2): 71–80. doi:10.1016/j.jdermsci.2005.04.001. PMID 15927452.
Newman B, Siminovitch KA (Jul 2005). "Recent advances in the genetics of inflammatory bowel disease". Current Opinion in Gastroenterology. 21 (4): 401–7. PMID 15930978.
Martinon F, Tschopp J (Aug 2005). "NLRs join TLRs as innate sensors of pathogens". Trends in Immunology. 26 (8): 447–54. doi:10.1016/j.it.2005.06.004. PMID 15967716.
Strober W, Murray PJ, Kitani A, Watanabe T (Jan 2006). "Signalling pathways and molecular interactions of NOD1 and NOD2". Nature Reviews. Immunology. 6 (1): 9–20. doi:10.1038/nri1747. PMID 16493424. S2CID 33505741.
Cavanaugh J (Jun 2006). "NOD2: ethnic and geographic differences". World Journal of Gastroenterology. 12 (23): 3673–7. doi:10.3748/wjg.v12.i23.3673. PMC 4087459. PMID 16773683.
Hugot JP (Aug 2006). "CARD15/NOD2 mutations in Crohn's disease". Annals of the New York Academy of Sciences. 1072 (1): 9–18. Bibcode:2006NYASA1072....9H. doi:10.1196/annals.1326.011. PMID 17057186. S2CID 24150549.
Vignal C, Singer E, Peyrin-Biroulet L, Desreumaux P, Chamaillard M (Apr 2007). "How NOD2 mutations predispose to Crohn's disease?". Microbes and Infection / Institut Pasteur. 9 (5): 658–63. doi:10.1016/j.micinf.2007.01.016. PMID 17379562.
Quaglietta L, te Velde A, Staiano A, Troncone R, Hommes DW (maj 2007). "Functional consequences of NOD2/CARD15 mutations in Crohn disease". Journal of Pediatric Gastroenterology and Nutrition. 44 (5): 529–39. doi:10.1097/MPG.0b013e31803815ee. PMID 17460484. S2CID 37476303.
van der Linde K, Boor PP, Houwing-Duistermaat JJ, Crusius BJ, Wilson PJ, Kuipers EJ, de Rooij FW (Jun 2007). "CARD15 mutations in Dutch familial and sporadic inflammatory bowel disease and an overview of European studies". European Journal of Gastroenterology & Hepatology. 19 (6): 449–59. doi:10.1097/01.meg.0000236887.44214.6a. PMID 17489054. S2CID 17766170.

Vanjski linkovi

Šablon:NOD-liki receptori

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000167207 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000055994 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid7809109-5] Gilberts EC, Greenstein AJ, Katsel P, Harpaz N, Greenstein RJ (Dec 1994). "Molecular evidence for two forms of Crohn disease". Proceedings of the National Academy of Sciences of the United States of America. 91 (26): 12721–4. Bibcode:1994PNAS...9112721G. doi:10.1073/pnas.91.26.12721. PMC 45511. PMID 7809109.

[pmid8587604-6] Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, Beaugerie L, Naom I, Dupas JL, Van Gossum A, Orholm M, Bonaiti-Pellie C, Weissenbach J, Mathew CG, Lennard-Jones JE, Cortot A, Colombel JF, Thomas G (Feb 1996). "Mapping of a susceptibility locus for Crohn's disease on chromosome 16". Nature. 379 (6568): 821–3. Bibcode:1996Natur.379..821H. doi:10.1038/379821a0. PMID 8587604. S2CID 4311407.

[7] Mahla RS, Reddy MC, Prasad DV, Kumar H (septembar 2013). "Sweeten PAMPs: Role of Sugar Complexed PAMPs in Innate Immunity and Vaccine Biology". Frontiers in Immunology. 4: 248. doi:10.3389/fimmu.2013.00248. PMC 3759294. PMID 24032031.

[pmid17057187-8] Kufer TA, Banks DJ, Philpott DJ (Aug 2006). "Innate immune sensing of microbes by Nod proteins". Annals of the New York Academy of Sciences. 1072 (1): 19–27. Bibcode:2006NYASA1072...19K. doi:10.1196/annals.1326.020. PMID 17057187. S2CID 20217610.

[entrez-9] "Entrez Gene: NOD2 nucleotide-binding oligomerization domain containing 2".

[pmid22319155-10] Nakagome S, Mano S, Kozlowski L, Bujnicki JM, Shibata H, Fukumaki Y, Kidd JR, Kidd KK, Kawamura S, Oota H (Jun 2012). "Crohn's disease risk alleles on the NOD2 locus have been maintained by natural selection on standing variation". Molecular Biology and Evolution. 29 (6): 1569–85. doi:10.1093/molbev/mss006. PMC 3697811. PMID 22319155.

[pmid11087742-11] Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G (Feb 2001). "Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB". The Journal of Biological Chemistry. 276 (7): 4812–8. doi:10.1074/jbc.M008072200. PMID 11087742.

[12] Sato H, Williams HR, Spagnolo P, Abdallah A, Ahmad T, Orchard TR, Copley SJ, Desai SR, Wells AU, du Bois RM, Welsh KI (Feb 2010). "CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis". Eur Respir J. 35 (2): 324–30. doi:10.1183/09031936.00010209. PMID 19679608.

[13] Zhao H, Jia M, Wang Z, Cheng Y, Luo Z, Chen Y, Xu X, Yang S, Tang Y (Jun 2015). "Association between NOD2 single nucleotide polymorphisms and Grade III-IV acute graft-versus-host disease: A meta-analysis". Hematology. 20 (5): 254–62. doi:10.1179/1607845414Y.0000000202. PMID 25248089. S2CID 206850232.

[pmid17131470-14] Radford-Smith G, Pandeya N (Nov 2006). "Associations between NOD2/CARD15 genotype and phenotype in Crohn's disease--Are we there yet?". World Journal of Gastroenterology. 12 (44): 7097–103. doi:10.3748/wjg.v12.i44.7097. PMC 4087769. PMID 17131470.

[pmid17096091-15] Kim TH, Payne U, Zhang X, Iwanaga Y, Davey MP, Rosenbaum JT, Inman RD (Jan 2007). "Altered host:pathogen interactions conferred by the Blau syndrome mutation of NOD2". Rheumatology International. 27 (3): 257–62. doi:10.1007/s00296-006-0250-0. PMID 17096091. S2CID 23739992.

[pmid15107016-16] Damiano JS, Oliveira V, Welsh K, Reed JC (Jul 2004). "Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses". The Biochemical Journal. 381 (Pt 1): 213–9. doi:10.1042/BJ20031506. PMC 1133779. PMID 15107016.

[pmid11472070-17] Damiano JS, Stehlik C, Pio F, Godzik A, Reed JC (Jul 2001). "CLAN, a novel human CED-4-like gene". Genomics. 75 (1–3): 77–83. doi:10.1006/geno.2001.6579. PMID 11472070.

[18] Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, Bose S (Oct 2009). "Activation of innate immune antiviral responses by Nod2". Nature Immunology. 10 (10): 1073–80. doi:10.1038/ni.1782. PMC 2752345. PMID 19701189.

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