CDCP1 on Dendritic Cells Contributes to the Development of a Model of Kawasaki Disease.
J Immunol
; 206(12): 2819-2827, 2021 06 15.
Article
en En
| MEDLINE
| ID: mdl-34099547
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Moléculas de Adhesión Celular
/
Modelos Animales de Enfermedad
/
Síndrome Mucocutáneo Linfonodular
/
Antígenos de Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Immunol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos