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Tim-1 mucin domain-mutant mice display exacerbated atherosclerosis.
Douna, Hidde; Smit, Virginia; van Puijvelde, Gijs H M; Kiss, Mate G; Binder, Christoph J; Bot, Llze; Kuchroo, Vijay K; Lichtman, Andrew H; Kuiper, Johan; Foks, Amanda C.
Afiliación
  • Douna H; Division of BioTherapeutics, LACDR, Leiden University, Einsteinweg 55, 2333CC, Leiden, the Netherlands.
  • Smit V; Division of BioTherapeutics, LACDR, Leiden University, Einsteinweg 55, 2333CC, Leiden, the Netherlands.
  • van Puijvelde GHM; Division of BioTherapeutics, LACDR, Leiden University, Einsteinweg 55, 2333CC, Leiden, the Netherlands.
  • Kiss MG; Department of Laboratory Medicine, Medical University of Vienna, Vienna, 1090, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
  • Binder CJ; Department of Laboratory Medicine, Medical University of Vienna, Vienna, 1090, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
  • Bot L; Division of BioTherapeutics, LACDR, Leiden University, Einsteinweg 55, 2333CC, Leiden, the Netherlands.
  • Kuchroo VK; Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
  • Lichtman AH; Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
  • Kuiper J; Division of BioTherapeutics, LACDR, Leiden University, Einsteinweg 55, 2333CC, Leiden, the Netherlands.
  • Foks AC; Division of BioTherapeutics, LACDR, Leiden University, Einsteinweg 55, 2333CC, Leiden, the Netherlands. Electronic address: a.c.foks@lacdr.leidenuniv.nl.
Atherosclerosis ; 352: 1-9, 2022 07.
Article en En | MEDLINE | ID: mdl-35636144
BACKGROUND AND AIMS: Increasing evidence has shown that immune checkpoint molecules of the T-cell immunoglobulin and mucin domain (Tim) family are associated with diverse physiologic and pathologic processes. Previous studies of the role of Tim-1 in atherosclerosis using anti-Tim-1 antibodies have yielded contradictory results. We thus aimed to investigate atherosclerosis development in Tim-1 deficient mice. METHODS: Mice with a specific loss of the Tim-1 mucin-domain (Tim-1Δmucin) and C57BL/6 (WT) mice received a single injection of a recombinant adeno-associated virus encoding murine Pcsk9 (rAAV2/8-D377Y-mPcsk9) and were fed a Western type diet for 13 weeks to introduce atherosclerosis. RESULTS: Tim-1Δmucin mice developed significantly larger lesions in the aortic root compared to WT mice, with significantly more macrophages and a trend towards a larger necrotic core. Furthermore, Tim-1Δmucin mice showed a significant loss of IL-10+ B cells and regulatory B cell subsets and increased pro-atherogenic splenic follicular B cells compared to WT mice. Moreover, Tim-1Δmucin mice displayed a dramatic reduction in Th2-associated immune response compared to controls but we did not observe any changes in humoral immunity. CONCLUSIONS: In summary, Tim-1Δmucin mice displayed a profound impairment in IL-10+ B cells and an imbalance in the Th1/Th2 ratio, which associated with exacerbated atherosclerosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aterosclerosis / Proproteína Convertasa 9 / Receptor Celular 1 del Virus de la Hepatitis A Límite: Animals Idioma: En Revista: Atherosclerosis Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aterosclerosis / Proproteína Convertasa 9 / Receptor Celular 1 del Virus de la Hepatitis A Límite: Animals Idioma: En Revista: Atherosclerosis Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Irlanda