دورية أكاديمية
أعرض في EDS

Murine MHC-Deficient Nonobese Diabetic Mice Carrying Human HLA-DQ8 Develop Severe Myocarditis and Myositis in Response to Anti-PD-1 Immune Checkpoint Inhibitor Cancer Therapy.

التفاصيل البيبلوغرافية
العنوان: Murine MHC-Deficient Nonobese Diabetic Mice Carrying Human HLA-DQ8 Develop Severe Myocarditis and Myositis in Response to Anti-PD-1 Immune Checkpoint Inhibitor Cancer Therapy.
المؤلفون: Racine JJ; The Jackson Laboratory, Bar Harbor, ME., Bachman JF; The Jackson Laboratory, Bar Harbor, ME., Zhang JG; The Jackson Laboratory, Bar Harbor, ME., Misherghi A; The Jackson Laboratory, Bar Harbor, ME.; College of the Atlantic, Bar Harbor, ME., Khadour R; The Jackson Laboratory, Bar Harbor, ME.; College of the Atlantic, Bar Harbor, ME., Kaisar S; Imperial College London, London, United Kingdom., Bedard O; The Jackson Laboratory, Bar Harbor, ME., Jenkins C; Imperial College London, London, United Kingdom., Abbott A; The Jackson Laboratory, Bar Harbor, ME., Forte E; The Jackson Laboratory, Bar Harbor, ME., Rainer P; Medical University of Graz, Graz, Austria.; BioTechMed Graz, Graz, Austria.; BKH St. Johann in Tirol, St. Johann in Tirol, Austria., Rosenthal N; The Jackson Laboratory, Bar Harbor, ME.; Imperial College London, London, United Kingdom., Sattler S; Imperial College London, London, United Kingdom.; Medical University of Graz, Graz, Austria., Serreze DV; The Jackson Laboratory, Bar Harbor, ME.
المصدر: Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Apr 15; Vol. 212 (8), pp. 1287-1306.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE
أسماء مطبوعة: Publication: Bethesda, MD : American Association of Immunologists
Original Publication: Baltimore : Williams & Wilkins, c1950-
مواضيع طبية MeSH: Myocarditis* , Diabetes Mellitus, Experimental* , Neoplasms* , Myositis*/chemically induced , Myositis*/pathology , HLA-DQ Antigens*, Humans ; Mice ; Animals ; Mice, Inbred NOD ; Immune Checkpoint Inhibitors/therapeutic use
مستخلص: Myocarditis has emerged as an immune-related adverse event of immune checkpoint inhibitor (ICI) cancer therapy associated with significant mortality. To ensure patients continue to safely benefit from life-saving cancer therapy, an understanding of fundamental immunological phenomena underlying ICI myocarditis is essential. We recently developed the NOD-cMHCI/II-/-.DQ8 mouse model that spontaneously develops myocarditis with lower mortality than observed in previous HLA-DQ8 NOD mouse strains. Our strain was rendered murine MHC class I and II deficient using CRISPR/Cas9 technology, making it a genetically clean platform for dissecting CD4+ T cell-mediated myocarditis in the absence of classically selected CD8+ T cells. These mice are highly susceptible to myocarditis and acute heart failure following anti-PD-1 ICI-induced treatment. Additionally, anti-PD-1 administration accelerates skeletal muscle myositis. Using histology, flow cytometry, adoptive transfers, and RNA sequencing analyses, we performed a thorough characterization of cardiac and skeletal muscle T cells, identifying shared and unique characteristics of both populations. Taken together, this report details a mouse model with features of a rare, but highly lethal clinical presentation of overlapping myocarditis and myositis following ICI therapy. This study sheds light on underlying immunological mechanisms in ICI myocarditis and provides the basis for further detailed analyses of diagnostic and therapeutic strategies.
(Copyright © 2024 by The American Association of Immunologists, Inc.)
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معلومات مُعتمدة: T32 AG062409 United States AG NIA NIH HHS; U54 OD020351 United States OD NIH HHS; P30 CA034196 United States CA NCI NIH HHS; U54 OD030187 United States OD NIH HHS; R01 DK095735 United States DK NIDDK NIH HHS; P20 GM103423 United States GM NIGMS NIH HHS
المشرفين على المادة: 0 (HLA-DQ8 antigen)
0 (Immune Checkpoint Inhibitors)
0 (HLA-DQ Antigens)
تواريخ الأحداث: Date Created: 20240301 Date Completed: 20240403 Latest Revision: 20240403
رمز التحديث: 20240403
مُعرف محوري في PubMed: PMC10984778
DOI: 10.4049/jimmunol.2300841
PMID: 38426910
قاعدة البيانات: MEDLINE
الوصف
تدمد:1550-6606
DOI:10.4049/jimmunol.2300841