دورية أكاديمية
أعرض في EDS

Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent "NoGlow" Mice.

التفاصيل البيبلوغرافية
العنوان: Overcoming Xenoantigen Immunity to Enable Cellular Tracking and Gene Regulation with Immune-competent "NoGlow" Mice.
المؤلفون: Trotter TN; Department of Surgery, Duke University, Durham, North Carolina., Wilson A; Department of Pathology, Duke University, Durham, North Carolina., McBane J; Department of Surgery, Duke University, Durham, North Carolina., Dagotto CE; Department of Surgery, Duke University, Durham, North Carolina., Yang XY; Department of Surgery, Duke University, Durham, North Carolina., Wei JP; Department of Surgery, Duke University, Durham, North Carolina., Lei G; Department of Surgery, Duke University, Durham, North Carolina., Thrash H; Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina., Snyder JC; Department of Surgery, Duke University, Durham, North Carolina.; Department of Cell Biology, Duke University, Durham, North Carolina., Lyerly HK; Department of Surgery, Duke University, Durham, North Carolina.; Department of Pathology, Duke University, Durham, North Carolina.; Department of Integrative Immunobiology, Duke University, Durham, North Carolina., Hartman ZC; Department of Surgery, Duke University, Durham, North Carolina.; Department of Pathology, Duke University, Durham, North Carolina.; Department of Integrative Immunobiology, Duke University, Durham, North Carolina.
المصدر: Cancer research communications [Cancer Res Commun] 2024 Apr 09; Vol. 4 (4), pp. 1050-1062.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9918281580506676 Publication Model: Print Cited Medium: Internet ISSN: 2767-9764 (Electronic) Linking ISSN: 27679764 NLM ISO Abbreviation: Cancer Res Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Philadelphia, Pennsylvania] : American Association for Cancer Research, [2021]-
مواضيع طبية MeSH: Antigens, Heterophile* , Cell Tracking*, Animals ; Mice ; Gene Expression Regulation ; Mice, Transgenic ; Disease Models, Animal
مستخلص: The ability to temporally regulate gene expression and track labeled cells makes animal models powerful biomedical tools. However, sudden expression of xenobiotic genes [e.g., GFP, luciferase (Luc), or rtTA3] can trigger inadvertent immunity that suppresses foreign protein expression or results in complete rejection of transplanted cells. Germline exposure to foreign antigens somewhat addresses these challenges; however, native fluorescence and bioluminescence abrogates the utility of reporter proteins and highly spatiotemporally restricted expression can lead to suboptimal xenoantigen tolerance. To overcome these unwanted immune responses and enable reliable cell tracking/gene regulation, we developed a novel mouse model that selectively expresses antigen-intact but nonfunctional forms of GFP and Luc, as well as rtTA3, after CRE-mediated recombination. Using tissue-specific CREs, we observed model and sex-based differences in immune tolerance to the encoded xenoantigens, illustrating the obstacles of tolerizing animals to foreign genes and validating the utility of these "NoGlow" mice to dissect mechanisms of central and peripheral tolerance. Critically, tissue unrestricted NoGlow mice possess no detectable background fluorescence or luminescence and exhibit limited adaptive immunity against encoded transgenic xenoantigens after vaccination. Moreover, we demonstrate that NoGlow mice allow tracking and tetracycline-inducible gene regulation of triple-transgenic cells expressing GFP/Luc/rtTA3, in contrast to transgene-negative immune-competent mice that eliminate these cells or prohibit metastatic seeding. Notably, this model enables de novo metastasis from orthotopically implanted, triple-transgenic tumor cells, despite high xenoantigen expression. Altogether, the NoGlow model provides a critical resource for in vivo studies across disciplines, including oncology, developmental biology, infectious disease, autoimmunity, and transplantation.
Significance: Multitolerant NoGlow mice enable tracking and gene manipulation of transplanted tumor cells without immune-mediated rejection, thus providing a platform to investigate novel mechanisms of adaptive immunity related to metastasis, immunotherapy, and tolerance.
(© 2024 The Authors; Published by the American Association for Cancer Research.)
References: Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2985-9. (PMID: 1532662)
Gene Ther. 1999 Jul;6(7):1305-12. (PMID: 10455440)
Cancer Cell. 2009 Aug 4;16(2):91-102. (PMID: 19647220)
Sci Rep. 2017 Aug 10;7(1):7715. (PMID: 28798322)
Oncoimmunology. 2018 Jan 19;7(5):e1421891. (PMID: 29721371)
Nat Genet. 2019 Jul;51(7):1113-1122. (PMID: 31209394)
Science. 1977 Aug 26;197(4306):893-5. (PMID: 887927)
Cancer Res. 2008 Feb 1;68(3):937-45. (PMID: 18245497)
Cell Rep. 2019 Sep 17;28(12):3092-3104.e5. (PMID: 31533033)
Cancer Res. 2020 Aug 1;80(15):3088-3100. (PMID: 32366475)
Elife. 2015 Mar 30;4:e05521. (PMID: 25821987)
Biochem Mol Biol Educ. 2011 Jul;39(4):309-15. (PMID: 21774060)
J Clin Invest. 2009 Nov;119(11):3311-21. (PMID: 19809157)
Cancer Cell. 2022 Jan 10;40(1):1-2. (PMID: 34861158)
Commun Biol. 2020 May 29;3(1):273. (PMID: 32472011)
Nat Commun. 2018 Feb 12;9(1):633. (PMID: 29434238)
Hum Gene Ther. 2002 Sep 1;13(13):1611-20. (PMID: 12228016)
Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14718-23. (PMID: 17785410)
Cell Rep. 2018 Oct 16;25(3):702-714.e6. (PMID: 30332649)
J Immunol. 2003 Dec 1;171(11):5787-94. (PMID: 14634087)
Sci Rep. 2017 May 19;7(1):2193. (PMID: 28526819)
Cell Mol Immunol. 2022 Jan;19(1):33-45. (PMID: 34417572)
PLoS One. 2014 Nov 04;9(11):e109956. (PMID: 25369133)
Biochemistry. 1999 Oct 5;38(40):13223-30. (PMID: 10529195)
Clin Exp Metastasis. 2003;20(2):135-41. (PMID: 12705634)
Clin Cancer Res. 2010 Mar 1;16(5):1466-77. (PMID: 20179231)
Front Oncol. 2018 Jul 20;8:268. (PMID: 30079312)
Mol Cancer Res. 2021 Oct;19(10):1699-1711. (PMID: 34131071)
J Dermatol. 2004 Apr;31(4):299-304. (PMID: 15187325)
Nucleic Acids Res. 1995 Dec 25;23(24):5080-1. (PMID: 8559668)
Biochemistry. 2003 Sep 9;42(35):10429-36. (PMID: 12950169)
Cancer Res. 2022 Jan 15;82(2):278-291. (PMID: 34666995)
Nucleic Acids Res. 1997 Nov 1;25(21):4323-30. (PMID: 9336464)
Front Immunol. 2021 Apr 22;12:676236. (PMID: 33968086)
Oncoimmunology. 2019 Mar 16;8(5):e1577127. (PMID: 31069138)
Oncotarget. 2021 Jan 05;12(1):1-3. (PMID: 33456706)
Cancer Immunol Res. 2015 Feb;3(2):149-60. (PMID: 25387892)
Cold Spring Harb Perspect Biol. 2012 Jun 01;4(6):. (PMID: 22661634)
Cancer Res. 2013 Jun 1;73(11):3470-80. (PMID: 23633491)
JCI Insight. 2023 Nov 22;8(22):. (PMID: 37847565)
Front Immunol. 2021 May 14;12:661875. (PMID: 34054826)
BMC Biotechnol. 2016 Jan 16;16:4. (PMID: 26772810)
Cell Rep. 2022 Mar 1;38(9):110447. (PMID: 35235800)
Luminescence. 2007 May-Jun;22(3):221-8. (PMID: 17286245)
Science. 1990 Jun 15;248(4961):1364-8. (PMID: 1694042)
Nat Cancer. 2022 Oct;3(10):1165-1180. (PMID: 36050483)
J Exp Med. 2017 Apr 3;214(4):895-904. (PMID: 28302645)
Nature. 2016 Dec 22;540(7634):588-592. (PMID: 27974798)
معلومات مُعتمدة: R01 CA238217 United States CA NCI NIH HHS; T32 CA009111 United States CA NCI NIH HHS; R01 CA255372 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Antigens, Heterophile)
تواريخ الأحداث: Date Created: 20240409 Date Completed: 20240410 Latest Revision: 20240411
رمز التحديث: 20240411
مُعرف محوري في PubMed: PMC11003454
DOI: 10.1158/2767-9764.CRC-24-0062
PMID: 38592453
قاعدة البيانات: MEDLINE
الوصف
تدمد:2767-9764
DOI:10.1158/2767-9764.CRC-24-0062