Innate Immune Cell Recovery Is Positively Regulated by NLRP12 during Emergency Hematopoiesis.
J Immunol
; 198(6): 2426-2433, 2017 03 15.
Article
en En
| MEDLINE
| ID: mdl-28159904
ABSTRACT
With enhanced concerns of terrorist attacks, dual exposure to radiation and thermal combined injury (RCI) has become a real threat with devastating immunosuppression. NLRP12, a member of the NOD-like receptor family, is expressed in myeloid and bone marrow cells and was implicated as a checkpoint regulator of inflammatory cytokines, as well as an inflammasome activator. We show that NLRP12 has a profound impact on hematopoietic recovery during RCI by serving as a checkpoint of TNF signaling and preventing hematopoietic apoptosis. Using a mouse model of RCI, increased NLRP12 expression was detected in target tissues. Nlrp12-/- mice exhibited significantly greater mortality, an inability to fight bacterial infection, heightened levels of proinflammatory cytokines, overt granulocyte/monocyte progenitor cell apoptosis, and failure to reconstitute peripheral myeloid populations. Anti-TNF Ab administration improved peripheral immune recovery. These data suggest that NLRP12 is essential for survival after RCI by regulating myelopoiesis and immune reconstitution.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Traumatismos Experimentales por Radiación
/
Quemaduras
/
Péptidos y Proteínas de Señalización Intracelular
/
Hematopoyesis
/
Inmunidad Innata
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Año:
2017
Tipo del documento:
Article