دورية أكاديمية
أعرض في EDS

Partial loss of Sorting Nexin 27 resembles age- and Down syndrome-associated T cell dysfunctions.

التفاصيل البيبلوغرافية
العنوان: Partial loss of Sorting Nexin 27 resembles age- and Down syndrome-associated T cell dysfunctions.
المؤلفون: Rodriguez-Rodriguez C; Department of Immunology and Oncology, Spanish National Centre for Biotechnology (CNB-CSIC), UAM Campus de Cantoblanco, Darwin 3, 28049, Madrid, Spain., González-Mancha N; Department of Immunology and Oncology, Spanish National Centre for Biotechnology (CNB-CSIC), UAM Campus de Cantoblanco, Darwin 3, 28049, Madrid, Spain., Ochoa-Echeverría A; Department of Immunology and Oncology, Spanish National Centre for Biotechnology (CNB-CSIC), UAM Campus de Cantoblanco, Darwin 3, 28049, Madrid, Spain., Liébana R; Department of Immunology and Oncology, Spanish National Centre for Biotechnology (CNB-CSIC), UAM Campus de Cantoblanco, Darwin 3, 28049, Madrid, Spain., Merida I; Department of Immunology and Oncology, Spanish National Centre for Biotechnology (CNB-CSIC), UAM Campus de Cantoblanco, Darwin 3, 28049, Madrid, Spain. imerida@cnb.csic.es.
المصدر: Immunity & ageing : I & A [Immun Ageing] 2024 Jan 02; Vol. 21 (1), pp. 2. Date of Electronic Publication: 2024 Jan 02.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101235427 Publication Model: Electronic Cited Medium: Print ISSN: 1742-4933 (Print) Linking ISSN: 17424933 NLM ISO Abbreviation: Immun Ageing Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, [2004]-
مستخلص: Background: Sorting Nexin 27 (SNX27)-retromer complex facilitates cargo recycling from endosomes to the plasma membrane. SNX27 downregulation in neurons, as the result of Trisomy 21 (T21), has been linked with cognitive deficits due to impairment of AMPA and NMDA receptor recycling. Studies in human T cell lines likewise demonstrated that SNX27 regulates the correct delivery of cargoes to the immune synapse limiting the activation of pro-inflammatory pathways. Nevertheless, the physiological consequences of partial SNX27 loss in T cell homeostasis are still unclear.
Results: In this study, we have explored the consequences of T cell specific partial SNX27 downregulation in mice. T cells with partial SNX27 deficiency show a marked deficit in the CD4 + T cell pool, a hallmark of aging in mice and humans, and a well-characterized comorbidity of individuals with Down syndrome (DS). When analyzed ex vivo, CD4 + T cells with partial SNX27 deletion demonstrate enhanced proliferation but diminished IL-2 production. In contrast, the CD8 + population show enhanced expression of pro-inflammatory cytokines and lytic enzymes.
Conclusions: This mouse model supports the relevance of SNX27 in the organization of the immune synapse, previously described in cell lines, as well as in the control of T cell homeostasis. Individuals with DS experiment an acceleration of the aging process, which particularly affects the immune and central nervous systems. Thus, we hypothesize that reduced SNX27 expression in DS could contribute to the dysregulation of these systems and further research in SNX27 will shed light on the molecular factors underlying the phenotypes observed in people with DS and its contribution to aging.
(© 2023. The Author(s).)
References: Sci Rep. 2017 Nov 27;7(1):16361. (PMID: 29180720)
Nat Immunol. 2013 May;14(5):428-36. (PMID: 23598398)
Nat Methods. 2012 Jun 28;9(7):676-82. (PMID: 22743772)
Traffic. 2017 Aug;18(8):491-504. (PMID: 28477369)
Mech Ageing Dev. 2023 Jun;212:111824. (PMID: 37236373)
Neuron. 2014 May 7;82(3):659-69. (PMID: 24811384)
Eur J Immunol. 2015 Mar;45(3):903-14. (PMID: 25472482)
Front Cell Dev Biol. 2020 Nov 27;8:595357. (PMID: 33330482)
Elife. 2016 Jul 29;5:. (PMID: 27472900)
Immunity. 2001 Nov;15(5):751-61. (PMID: 11728337)
Front Immunol. 2022 Jan 12;12:814570. (PMID: 35095913)
Science. 2007 Mar 23;315(5819):1687-91. (PMID: 17332376)
Cell. 2013 Jun 6;153(6):1194-217. (PMID: 23746838)
Sci Transl Med. 2022 Jan 12;14(627):eabi4888. (PMID: 35020411)
Nat Commun. 2021 May 11;12(1):2715. (PMID: 33976157)
Proc Natl Acad Sci U S A. 2019 Nov 26;116(48):24231-24241. (PMID: 31699819)
Nat Cell Biol. 2011 Dec 22;14(1):29-37. (PMID: 22193161)
Microbes Infect. 2010 Oct;12(11):799-808. (PMID: 20685340)
Cell Rep. 2019 Nov 12;29(7):1893-1908.e4. (PMID: 31722205)
Immun Ageing. 2022 Mar 23;19(1):16. (PMID: 35321714)
Acta Paediatr. 2007 Oct;96(10):1479-82. (PMID: 17727689)
Nat Cell Biol. 2013 May;15(5):461-71. (PMID: 23563491)
J Exp Med. 1997 Oct 20;186(8):1223-32. (PMID: 9334361)
Subcell Biochem. 2014;80:197-220. (PMID: 24798013)
Nat Rev Mol Cell Biol. 2008 Jul;9(7):574-82. (PMID: 18523436)
Semin Immunol. 2018 Dec;40:1-5. (PMID: 30392751)
Sci Signal. 2018 Apr 17;11(526):. (PMID: 29666307)
J Immunol. 2011 Sep 15;187(6):3422-30. (PMID: 21856934)
Alzheimers Dement (N Y). 2023 May 22;9(2):e12393. (PMID: 37228575)
Sci Rep. 2016 Aug 02;6:30842. (PMID: 27480406)
Mol Cell Biol. 2011 Apr;31(8):1734-47. (PMID: 21300787)
Nature. 2006 Sep 28;443(7110):462-5. (PMID: 17006514)
Nat Immunol. 2018 Jan;19(1):10-19. (PMID: 29242543)
Crit Rev Immunol. 2014;34(2):121-46. (PMID: 24940912)
Cell Rep. 2014 Nov 6;9(3):1023-33. (PMID: 25437557)
J Immunol. 2014 Sep 15;193(6):2622-9. (PMID: 25193936)
Immunol Rev. 2002 Nov;189:152-60. (PMID: 12445272)
Nature. 2011 Aug 31;477(7362):90-4. (PMID: 21886162)
Nat Med. 2013 Apr;19(4):473-80. (PMID: 23524343)
Acta Paediatr. 2022 Oct;111(10):2025-2028. (PMID: 35842744)
معلومات مُعتمدة: 713673 HORIZON EUROPE Marie Sklodowska-Curie Actions; 100010434 'la Caixa' Foundation; PID2019-108357RB-100/AEI/10.13039/501100011033 Ministerio de Ciencia e Innovación; PID2019-108357RB-100/AEI/10.13039/501100011033 Ministerio de Ciencia e Innovación; PID2019-108357RB-100/AEI/10.13039/501100011033 Ministerio de Ciencia e Innovación
فهرسة مساهمة: Keywords: Aging; Cytokines; Down syndrome; Inflammation; Lymphocyte; SNX27
تواريخ الأحداث: Date Created: 20240103 Latest Revision: 20240106
رمز التحديث: 20240106
مُعرف محوري في PubMed: PMC10759489
DOI: 10.1186/s12979-023-00402-3
PMID: 38166948
قاعدة البيانات: MEDLINE
الوصف
تدمد:1742-4933
DOI:10.1186/s12979-023-00402-3