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Innate immune cell recovery is positively regulated by NLRP12 during emergency hematopoiesis
Linz, B. M. L., Neely, C. J., Kartchner, L. B., Mendoza, A. E., Khoury, A. L., Truax, A., Sempowski, G., Eitas, T., Brickey, J., Ting, J. P. Y., Cairns, B. A., & Maile, R. (2017). Innate immune cell recovery is positively regulated by NLRP12 during emergency hematopoiesis. Journal of Immunology, 198(6), 2426-2433. https://doi.org/10.4049/jimmunol.1601048
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.
