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CDCP1 on Dendritic Cells Contributes to the Development of a Model of Kawasaki Disease.

Abstract
The etiology and pathology of Kawasaki disease (KD) remain elusive. Cub domain-containing protein 1 (CDCP1), a cell-surface protein that confers poor prognosis of patients with certain solid tumors, was recently identified as one of the most significantly upregulated genes in SARS-CoV-2-infected children who developed systemic vasculitis, a hallmark of KD. However, a potential role of CDCP1 in KD has not previously been explored. In this study, we found that CDCP1 knockout (KO) mice exhibited attenuated coronary and aortic vasculitis and decreased serum Candida albicans water-soluble fraction (CAWS)-specific IgM/IgG2a and IL-6 concentrations compared with wild-type mice in an established model of KD induced by CAWS administration. CDCP1 expression was not detectable in cardiomyocytes, cardio fibroblasts, or coronary endothelium, but constitutive expression of CDCP1 was observed on dendritic cells (DCs) and was upregulated by CAWS stimulation. CAWS-induced IL-6 production was significantly reduced in CDCP1 KO DCs, in association with impaired Syk-MAPK signaling pathway activation. These novel findings suggest that CDCP1 might regulate KD development by modulating IL-6 production from DCs via the Syk-MAPK signaling pathway.
AuthorsYu Lun, Nozha Borjini, Noriko N Miura, Naohito Ohno, Nora G Singer, Feng Lin
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 206 Issue 12 Pg. 2819-2827 (06 15 2021) ISSN: 1550-6606 [Electronic] United States
PMID34099547 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021 by The American Association of Immunologists, Inc.
Chemical References
  • Antigens, Neoplasm
  • CDCP1 protein, mouse
  • Cell Adhesion Molecules
Topics
  • Animals
  • Antigens, Neoplasm (immunology)
  • Cell Adhesion Molecules (deficiency, immunology)
  • Cells, Cultured
  • Dendritic Cells (immunology)
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mucocutaneous Lymph Node Syndrome (immunology)

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