| Autor: |
Sempowski, Gregory, Eitas, Timothy, Linz, Brandon M. L., Kartchner, Laurel B., Maile, Robert, Cairns, Bruce A., Mendoza, April E., Khoury, Amal L., Neely, Crystal J., Ting, Jenny P. Y., Brickey, June, Truax, Agnieszka |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| DOI: |
10.17615/ah93-9c19 |
| Popis: |
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 has been 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, inability to fight bacterial infection, heightened levels of pro-inflammatory cytokines, overt granulocyte/monocyte progenitor cell apoptosis and failure to reconstitute peripheral myeloid populations. Anti-TNF antibody administration improved peripheral immune recovery. These data suggest that NLRP12 is essential for survival after RCI by regulating myelopoiesis and immune reconstitution. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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