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.
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Brandon M L
0000-0003-1899-1837
BM
Linz
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Crystal J
CJ
Neely
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Laurel B
LB
Kartchner
Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
April E
AE
Mendoza
Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Amal L
0000-0002-6501-7167
AL
Khoury
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Agnieszka
A
Truax
Human Vaccine Institute, Duke University, Durham, NC 27708; and.
Gregory
0000-0003-0391-6594
G
Sempowski
Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.|Host Defense Discovery Performance Unit, GlaxoSmithKline, Research Triangle Park, NC 27709.
Timothy
T
Eitas
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
June
J
Brickey
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Jenny P Y
0000-0002-7846-0395
JP
Ting
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.|Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Bruce A
BA
Cairns
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; robmaile@med.unc.edu.|Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Robert
0000-0002-9126-4188
R
Maile
D000818:Animals; D017209:Apoptosis; D002056:Burns / Q000276:immunology*; D000066673:Cell Self Renewal; D016207:Cytokines / Q000378:metabolism; D006410:Hematopoiesis; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011833:Radiation Injuries, Experimental / Q000276:immunology*; D015398:Signal Transduction; D014916:Whole-Body Irradiation
D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D047908:Intracellular Signaling Peptides and Proteins; C553199:NLRP12 protein, mouse