Pathogenic Interleukin-10 Receptor Alpha Variants in Humans - Balancing Natural Selection and Clinical Implications.
IL-10
IL10RA
inflammatory bowel disease
natural selection
Journal
Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
28
12
2021
accepted:
09
09
2022
pubmed:
13
11
2022
medline:
4
2
2023
entrez:
12
11
2022
Statut:
ppublish
Résumé
Balancing natural selection is a process by which genetic variants arise in populations that are beneficial to heterozygous carriers, but pathogenic when homozygous. We systematically investigated the prevalence, structural, and functional consequences of pathogenic IL10RA variants that are associated with monogenic inflammatory bowel disease. We identify 36 non-synonymous and non-sense variants in the IL10RA gene. Since the majority of these IL10RA variants have not been functionally characterized, we performed a systematic screening of their impact on STAT3 phosphorylation upon IL-10 stimulation. Based on the geographic accumulation of confirmed pathogenic IL10RA variants in East Asia and in Northeast China, the distribution of infectious disorders worldwide, and the functional evidence of IL-10 signaling in the pathogenesis, we identify Schistosoma japonicum infection as plausible selection pressure driving variation in IL10RA. Consistent with this is a partially augmented IL-10 response in peripheral blood mononuclear cells from heterozygous variant carriers. A parasite-driven heterozygote advantage through reduced IL-10 signaling has implications for health care utilization in regions with high allele frequencies and potentially indicates pathogen eradication strategies that target IL-10 signaling.
Identifiants
pubmed: 36370291
doi: 10.1007/s10875-022-01366-7
pii: 10.1007/s10875-022-01366-7
pmc: PMC9892166
doi:
Substances chimiques
Receptors, Interleukin-10
0
Interleukin-10
130068-27-8
Interleukin-10 Receptor alpha Subunit
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
495-511Subventions
Organisme : Wellcome Trust
ID : 106169/ZZ14/Z
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
Références
Epidemics. 2013 Mar;5(1):1-10
pubmed: 23438426
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W299-302
pubmed: 15980475
Diagn Pathol. 2018 Feb 27;13(1):17
pubmed: 29482573
Nat Rev Genet. 2010 Jan;11(1):17-30
pubmed: 19953080
Immunology. 2016 Sep;149(1):25-34
pubmed: 27242265
Immunity. 2001 Jul;15(1):35-46
pubmed: 11485736
Nat Rev Dis Primers. 2018 Mar 15;4:18010
pubmed: 29542687
Rev Med Virol. 2014 Mar;24(2):90-102
pubmed: 24310908
Inflamm Bowel Dis. 2017 Apr;23(4):578-590
pubmed: 28267044
N Engl J Med. 2009 Feb 12;360(7):692-8
pubmed: 19213682
J Exp Med. 2009 Jun 8;206(6):1395-408
pubmed: 19468064
Exp Mol Med. 2014 Jan 31;46:e74
pubmed: 24480801
Mol Ther. 2012 Jun;20(6):1242-50
pubmed: 22434135
PLoS One. 2011;6(11):e27464
pubmed: 22087322
N Engl J Med. 2002 Apr 18;346(16):1212-20
pubmed: 11961151
Nat Genet. 2015 Sep;47(9):979-986
pubmed: 26192919
Gigascience. 2018 Jul 1;7(7):
pubmed: 30010766
Parasitol Res. 2016 Dec;115(12):4559-4571
pubmed: 27640151
Gastroenterology. 2021 Apr;160(5):1546-1557
pubmed: 33359885
J Gen Virol. 2014 Feb;95(Pt 2):245-262
pubmed: 24225498
Trends Parasitol. 2014 Mar;30(3):141-50
pubmed: 24433721
Front Immunol. 2013 Apr 15;4:89
pubmed: 23596444
Gastroenterology. 2012 Aug;143(2):347-55
pubmed: 22549091
J Exp Med. 2001 Nov 19;194(10):1497-506
pubmed: 11714756
Nat Rev Immunol. 2019 Apr;19(4):205-217
pubmed: 30770905
Annu Rev Genomics Hum Genet. 2013;14:215-43
pubmed: 23724903
Malar J. 2013 Sep 11;12:317
pubmed: 24025776
Curr Top Microbiol Immunol. 2014;380:191-212
pubmed: 25004819
Structure. 2005 Apr;13(4):551-64
pubmed: 15837194
Science. 2000 Aug 25;289(5483):1352-5
pubmed: 10958782
Front Immunol. 2019 May 15;10:1095
pubmed: 31156641
Biochim Biophys Acta. 2014 Apr 4;1841(4):495-504
pubmed: 24388961
Lancet Infect Dis. 2018 Mar;18(3):e64-e75
pubmed: 29111156
Nucleic Acids Res. 2021 Jan 8;49(D1):D1225-D1232
pubmed: 33095885
Sci Rep. 2017 May 3;7(1):1377
pubmed: 28469196
Gastroenterology. 2022 Mar;162(3):859-876
pubmed: 34780721
PLoS Negl Trop Dis. 2014 Oct 02;8(10):e3206
pubmed: 25275395
Nat Microbiol. 2019 Mar;4(3):429-437
pubmed: 30617349
N Engl J Med. 2009 Nov 19;361(21):2033-45
pubmed: 19890111
BMC Gastroenterol. 2016 Jan 28;16:10
pubmed: 26822028
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Nat Rev Genet. 2014 Jun;15(6):379-93
pubmed: 24776769
Parasite Immunol. 2012 Aug-Sep;34(8-9):430-9
pubmed: 22712636
Int J Parasitol. 2016 Nov;46(12):799-808
pubmed: 27590846
Nat Rev Gastroenterol Hepatol. 2015 Dec;12(12):720-7
pubmed: 26323879
BMJ. 2018 Feb 5;360:j5910
pubmed: 29437562
Annu Rev Genomics Hum Genet. 2007;8:163-92
pubmed: 17492906
Nucleic Acids Res. 2019 Jan 8;47(D1):D886-D894
pubmed: 30371827
Nat Rev Dis Primers. 2018 Aug 9;4(1):13
pubmed: 30093684
Parasite Immunol. 2010 Jul;32(7):473-8
pubmed: 20591117
Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2668-73
pubmed: 24550294
Inflamm Bowel Dis. 2019 Mar 14;25(4):756-766
pubmed: 30212871
Am J Hum Genet. 2016 Oct 6;99(4):877-885
pubmed: 27666373
Structure. 2016 Jun 7;24(6):897-905
pubmed: 27133025
Nat Immunol. 2020 Aug;21(8):857-867
pubmed: 32601469
J Immunol. 2007 Jun 15;178(12):7520-4
pubmed: 17548585
Nat Genet. 2014 Mar;46(3):310-5
pubmed: 24487276
PLoS Genet. 2011 Nov;7(11):e1002355
pubmed: 22072984
Nat Genet. 2012 Feb 05;44(3):257-9
pubmed: 22306650
J Immunol. 2017 Jun 15;198(12):4716-4727
pubmed: 28476935
Acta Trop. 2021 May;217:105852
pubmed: 33548205
Lancet. 2006 Sep 23;368(9541):1106-18
pubmed: 16997665
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Infect Genet Evol. 2018 Sep;63:62-72
pubmed: 29763671
Nature. 2002 Dec 5;420(6915):502-7
pubmed: 12466842
Nature. 2019 Apr;568(7751):244-248
pubmed: 30836379
PLoS One. 2011;6(6):e21152
pubmed: 21695175
Clin Microbiol Rev. 2001 Apr;14(2):270-95
pubmed: 11292639
J Pediatr Gastroenterol Nutr. 2021 Mar 1;72(3):456-473
pubmed: 33346580
Parasite Immunol. 2018 Oct;40(10):e12577
pubmed: 30074250
Korean J Parasitol. 2007 Jun;45(2):95-102
pubmed: 17570971
Lancet Gastroenterol Hepatol. 2020 Jan;5(1):17-30
pubmed: 31648971
J Crohns Colitis. 2016 Nov;10(11):1366-1371
pubmed: 27177777
Lancet. 2010 Oct 9;376(9748):1272
pubmed: 20934598
Lancet. 2018 Dec 23;390(10114):2769-2778
pubmed: 29050646
Bioinformatics. 2003 Jan;19(1):163-4
pubmed: 12499312
J Gastroenterol Hepatol. 2011 Apr;26(4):694-9
pubmed: 21155887
Database (Oxford). 2020 Jan 1;2020:
pubmed: 32348452