Innate Immune Cell Recovery Is Positively Regulated by NLRP12 during Emergency Hematopoiesis.
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.
Linz, BML; Neely, CJ; Kartchner, LB; Mendoza, AE; Khoury, AL; Truax, A; Sempowski, G; Eitas, T; Brickey, J; Ting, JPY; Cairns, BA; Maile, R
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