دورية أكاديمية
أعرض في EDS

HLA-C expression in extravillous trophoblasts is determined by an ELF3-NLRP2/NLRP7 regulatory axis.

التفاصيل البيبلوغرافية
العنوان: HLA-C expression in extravillous trophoblasts is determined by an ELF3-NLRP2/NLRP7 regulatory axis.
المؤلفون: Gu B; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138., Le GH; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138., Herrera S; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138., Blair SJ; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138., Meissner TB; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.; Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02115.; Department of Surgery, Harvard Medical School, Boston, MA 02115., Strominger JL; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jul 30; Vol. 121 (31), pp. e2404229121. Date of Electronic Publication: 2024 Jul 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Adaptor Proteins, Signal Transducing*/metabolism , Adaptor Proteins, Signal Transducing*/genetics , Apoptosis Regulatory Proteins* , Extravillous Trophoblasts* , HLA-C Antigens*/metabolism , HLA-C Antigens*/genetics , Trophoblasts*/metabolism, Female ; Humans ; Pregnancy ; Cell Line, Tumor ; Gene Expression Regulation ; Proto-Oncogene Proteins c-ets/metabolism ; Proto-Oncogene Proteins c-ets/genetics ; Transcription Factors/metabolism ; Transcription Factors/genetics ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism
مستخلص: The distinct human leukocyte antigen (HLA) class I expression pattern of human extravillous trophoblasts (EVT) endows them with unique tolerogenic properties that enable successful pregnancy. Nevertheless, how this process is elaborately regulated remains elusive. Previously, E74 like ETS transcription factor 3 (ELF3) was identified to govern high-level HLA-C expression in EVT. In the present study, ELF3 is found to bind to the enhancer region of two adjacent NOD-like receptor (NLR) genes, NLR family pyrin domain-containing 2 and 7 (NLRP2, NLRP7). Notably, our analysis of ELF3-deficient JEG-3 cells, a human choriocarcinoma cell line widely used to study EVT biology, suggests that ELF3 transactivates NLRP7 while suppressing the expression of NLRP2. Moreover, we find that NLRP2 and NLRP7 have opposing effects on HLA-C expression, thus implicating them in immune evasion at the maternal-fetal interface. We confirmed that NLRP2 suppresses HLA-C levels and described a unique role for NLRP7 in promoting HLA-C expression in JEG-3. These results suggest that these two NLR genes, which arose via gene duplication in primates, are fine-tuned by ELF3 yet have acquired divergent functions to enable proper expression levels of HLA-C in EVT, presumably through modulating the degradation kinetics of IkBα. Targeting the ELF3-NLRP2/NLRP7-HLA-C axis may hold therapeutic potential for managing pregnancy-related disorders, such as recurrent hydatidiform moles and fetal growth restriction, and thus improve placental development and pregnancy outcomes.
Competing Interests: Competing interests statement:The authors declare no competing interest.
References: Nat Struct Mol Biol. 2013 Sep;20(9):1131-9. (PMID: 23934149)
Nature. 2012 Jan 18;481(7381):278-86. (PMID: 22258606)
Front Immunol. 2019 Dec 09;10:2730. (PMID: 31921098)
Trends Immunol. 2017 Apr;38(4):272-286. (PMID: 28279591)
Proc Natl Acad Sci U S A. 2021 Mar 2;118(9):. (PMID: 33622787)
PLoS Genet. 2018 Jan 12;14(1):e1007163. (PMID: 29329284)
J Immunol. 2007 Dec 15;179(12):8519-24. (PMID: 18056399)
Nat Commun. 2017 May 11;8:15203. (PMID: 28492230)
J Mol Evol. 2014 Apr;78(3-4):194-201. (PMID: 24615281)
Nature. 2018 Nov;563(7731):347-353. (PMID: 30429548)
Proc Natl Acad Sci U S A. 2017 Nov 7;114(45):E9579-E9588. (PMID: 29078328)
Mol Reprod Dev. 2009 Feb;76(2):151-9. (PMID: 18509866)
Cells. 2023 Mar 09;12(6):. (PMID: 36980199)
Cell. 1993 Oct 8;75(1):135-46. (PMID: 8402893)
Science. 1994 Jul 1;265(5168):106-9. (PMID: 8016643)
PLoS One. 2008 Jul 23;3(7):e2755. (PMID: 18648497)
Int J Biol Sci. 2022 Jun 13;18(10):4043-4052. (PMID: 35844794)
Early Pregnancy (Cherry Hill). 2001 Jan;5(1):67-9. (PMID: 11753519)
Biochem Biophys Res Commun. 2012 Feb 24;418(4):786-91. (PMID: 22310711)
J Med Genet. 2018 Jul;55(7):497-504. (PMID: 29574422)
Hum Mutat. 2022 Dec;43(12):1732-1744. (PMID: 35842788)
Eur J Hum Genet. 2017 Aug;25(8):924-929. (PMID: 28561018)
Hum Mol Genet. 2014 Feb 1;23(3):706-16. (PMID: 24105472)
HLA. 2018 Nov;92(5):288-297. (PMID: 30270560)
BMC Evol Biol. 2009 Aug 14;9:202. (PMID: 19682372)
Hum Mol Genet. 1999 Apr;8(4):667-71. (PMID: 10072436)
Biol Reprod. 2017 Apr 1;96(4):831-842. (PMID: 28340094)
J Immunol. 2002 Oct 15;169(8):4088-93. (PMID: 12370334)
Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13794-9. (PMID: 20639463)
Proc Natl Acad Sci U S A. 2016 May 10;113(19):5364-9. (PMID: 27078102)
Immunology. 2021 Aug;163(4):363-376. (PMID: 34021586)
Biomedicines. 2022 Jan 24;10(2):. (PMID: 35203462)
HLA. 2018 Nov;92(5):271-278. (PMID: 30232844)
Nat Immunol. 2011 Feb;12(2):121-8. (PMID: 21245903)
J Mol Med (Berl). 2019 Mar;97(3):355-367. (PMID: 30617930)
Nat Rev Immunol. 2019 Aug;19(8):477-489. (PMID: 31036962)
Trends Cell Biol. 2021 Nov;31(11):924-939. (PMID: 34284921)
J Exp Clin Cancer Res. 2021 Apr 10;40(1):126. (PMID: 33838681)
Nat Rev Immunol. 2023 Oct;23(10):635-654. (PMID: 36973360)
Placenta. 2016 Jan;37:45-55. (PMID: 26604129)
Reprod Biol Endocrinol. 2017 Aug 15;15(1):66. (PMID: 28810880)
Cell Discov. 2020 Jun 9;6:36. (PMID: 32550001)
Nat Genet. 2006 Mar;38(3):300-2. (PMID: 16462743)
Cell Death Dis. 2020 Aug 19;11(8):658. (PMID: 32814763)
Immunology. 1986 Dec;59(4):595-601. (PMID: 3804380)
J Biol Chem. 2004 Jun 11;279(24):25241-50. (PMID: 15075319)
معلومات مُعتمدة: R01 AI145862 United States AI NIAID NIH HHS; R01AI145862 United States GF NIH HHS
فهرسة مساهمة: Keywords: ELF3; HLA-C; NLRP7; gene regulation; immune tolerance
المشرفين على المادة: 0 (Adaptor Proteins, Signal Transducing)
0 (Apoptosis Regulatory Proteins)
0 (HLA-C Antigens)
0 (NLRP2 protein, human)
0 (NLRP7 protein, human)
0 (Proto-Oncogene Proteins c-ets)
0 (Transcription Factors)
0 (ELF3 protein, human)
0 (DNA-Binding Proteins)
تواريخ الأحداث: Date Created: 20240725 Date Completed: 20240725 Latest Revision: 20240804
رمز التحديث: 20240804
مُعرف محوري في PubMed: PMC11295039
DOI: 10.1073/pnas.2404229121
PMID: 39052836
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.2404229121