Cutting edge: NLRP12 controls dendritic and myeloid cell migration to affect contact hypersensitivity.
Nucleotide-binding domain leucine-rich repeat (NLR) proteins are regulators of inflammation and immunity. Although first described 8 y ago, a physiologic role for NLRP12 has remained elusive until now. We find that murine Nlrp12, an NLR linked to atopic dermatitis and hereditary periodic fever in humans, is prominently expressed in dendritic cells (DCs) and neutrophils. Nlrp12-deficient mice exhibit attenuated inflammatory responses in two models of contact hypersensitivity that exhibit features of allergic dermatitis. This cannot be attributed to defective Ag processing/presentation, inflammasome activation, or measurable changes in other inflammatory cytokines. Rather, Nlrp12(-/-) DCs display a significantly reduced capacity to migrate to draining lymph nodes. Both DCs and neutrophils fail to respond to chemokines in vitro. These findings indicate that NLRP12 is important in maintaining neutrophils and peripheral DCs in a migration-competent state.
Arthur
Janelle C
JC
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Lich
John D
JD
Ye
Zhengmao
Z
Allen
Irving C
IC
Gris
Denis
D
Wilson
Justin E
JE
Schneider
Monika
M
Roney
Kelly E
KE
O'Connor
Brian P
BP
Moore
Chris B
CB
Morrison
Amy
A
Sutterwala
Fayyaz S
FS
Bertin
John
J
Koller
Beverly H
BH
Liu
Zhi
Z
Ting
Jenny P-Y
JP
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D016133:Polymerase Chain Reaction
D047908:Intracellular Signaling Peptides and Proteins; C553199:NLRP12 protein, mouse