title: Characterization of NLRP12 during the development of allergic airway disease in mice.
abstract: Among the 22 members of the nucleotide binding-domain, leucine rich repeat-containing (NLR) family, less than half have been functionally characterized. Of those that have been well studied, most form caspase-1 activating inflammasomes. NLRP12 is a unique NLR that has been shown to attenuate inflammatory pathways in biochemical assays and mediate the lymph node homing of activated skin dendritic cells in contact hypersensitivity responses. Since the mechanism between these two important observations remains elusive, we further evaluated the contribution of NLRP12 to organ specific adaptive immune responses by focusing on the lung, which, like skin, is exposed to both exogenous and endogenous inflammatory agents. In models of allergic airway inflammation induced by either acute ovalbumin (OVA) exposure or chronic house dust mite (HDM) antigen exposure, Nlrp12(-/-) mice displayed subtle differences in eosinophil and monocyte infiltration into the airways. However, the overall development of allergic airway disease and airway function was not significantly altered by NLRP12 deficiency. Together, the combined data suggest that NLRP12 does not play a vital role in regulating Th2 driven airway inflammation using common model systems that are physiologically relevant to human disease. Thus, the allergic airway inflammation models described here should be appropriate for subsequent studies that seek to decipher the contribution of NLRP12 in mediating the host response to agents associated with asthma exacerbation.
authors.affiliation: Lineberger Comprehensive Cancer Center, Institute of Inflammatory Diseases and Center for Translational Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Irving C
authors.initials: IC
authors.lastname: Allen
authors.forename: John D
authors.initials: JD
authors.lastname: Lich
authors.forename: Janelle C
authors.initials: JC
authors.lastname: Arthur
authors.forename: Corey M
authors.initials: CM
authors.lastname: Jania
authors.forename: Reid A
authors.initials: RA
authors.lastname: Roberts
authors.forename: Justin B
authors.initials: JB
authors.lastname: Callaway
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Tilley
authors.forename: Jenny P-Y
authors.initials: JP
authors.lastname: Ting
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000009:adverse effects / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D012140:Respiratory Tract Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D039741:Antigens, Dermatophagoides; D047908:Intracellular Signaling Peptides and Proteins; C553199:NLRP12 protein, mouse; D010047:Ovalbumin