Innate immune cell recovery is positively regulated by NLRP12 during emergency hematopoiesis
BML Linz, CJ Neely, LB Kartchner… - The Journal of …, 2017 - journals.aai.org
BML Linz, CJ Neely, LB Kartchner, AE Mendoza, AL Khoury, A Truax, G Sempowski, T Eitas…
The Journal of Immunology, 2017•journals.aai.orgWith 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 …
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 …
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.
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