Cutting Edge: Dysregulated CARD9 Signaling in Neutrophils Drives Inflammation in a Mouse Model of Neutrophilic Dermatoses.
J Immunol
; 201(6): 1639-1644, 2018 09 15.
Article
en En
| MEDLINE
| ID: mdl-30082320
ABSTRACT
Mice homozygous for the Y208N amino acid substitution in the carboxy terminus of SHP-1 (referred to as Ptpn6spin mice) spontaneously develop a severe inflammatory disease resembling neutrophilic dermatosis in humans. Disease in Ptpn6spin mice is characterized by persistent footpad swelling and suppurative inflammation. Recently, in addition to IL-1α and IL-1R signaling, we demonstrated a pivotal role for RIPK1, TAK1, and ASK1 in promoting inflammatory disease in Ptpn6spin mice. In the current study we have identified a previously unknown role for CARD9 signaling as a critical regulator for Ptpn6spin-mediated footpad inflammation. Genetic deletion of CARD9 significantly rescued the Ptpn6spin-mediated footpad inflammation. Mechanistically, enhanced IL-1α-mediated signaling in Ptpn6spin mice neutrophils was dampened in Ptpn6spinCard9-/- mice. Collectively, this study identifies SHP-1 and CARD9 cross-talk as a novel regulator of IL-1α-driven inflammation and opens future avenues for finding novel drug targets to treat neutrophilic dermatosis in humans.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Dermatitis
/
Proteínas Adaptadoras de Señalización CARD
/
Neutrófilos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2018
Tipo del documento:
Article