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

First Author  Lun Y Year  2021
Journal  J Immunol Volume  206
Issue  12 Pages  2819-2827
PubMed ID  34099547 Mgi Jnum  J:322209
Mgi Id  MGI:6727762 Doi  10.4049/jimmunol.2001406
Citation  Lun Y, et al. (2021) CDCP1 on Dendritic Cells Contributes to the Development of a Model of Kawasaki Disease. J Immunol
abstractText  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.
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