title: Cutting edge: NLRP12 controls dendritic and myeloid cell migration to affect contact hypersensitivity.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Janelle C
authors.initials: JC
authors.lastname: Arthur
authors.forename: John D
authors.initials: JD
authors.lastname: Lich
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Ye
authors.forename: Irving C
authors.initials: IC
authors.lastname: Allen
authors.forename: Denis
authors.initials: D
authors.lastname: Gris
authors.forename: Justin E
authors.initials: JE
authors.lastname: Wilson
authors.forename: Monika
authors.initials: M
authors.lastname: Schneider
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Roney
authors.forename: Brian P
authors.initials: BP
authors.lastname: O'Connor
authors.forename: Chris B
authors.initials: CB
authors.lastname: Moore
authors.forename: Amy
authors.initials: A
authors.lastname: Morrison
authors.forename: Fayyaz S
authors.initials: FS
authors.lastname: Sutterwala
authors.forename: John
authors.initials: J
authors.lastname: Bertin
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Koller
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.forename: Jenny P-Y
authors.initials: JP
authors.lastname: Ting
mesh_terms: 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
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C553199:NLRP12 protein, mouse