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.
Highlights
NLRP12 ( MONARCH-1/PYPAF7) is a member of the nucleotide binding domain, leucine rich repeats-containing family (NLR) of proteins, which sense pathogens and pathogen products in the cell cytoplasm [1]
Nlrp122/2 mice were found to have defective dendritic cell homing to the lymph node, which resulted in attenuated contact hypersensitivity to cutaneously applied allergens [8]
OVA sensitization followed by airway challenges with the antigen resulted in a significant increase in bronchoalveolar lavage fluid (BALF) cellularity in both Nlrp122/2 and wild type animals (Figure 1B)
Summary
NLRP12 ( MONARCH-1/PYPAF7) is a member of the nucleotide binding domain, leucine rich repeats-containing family (NLR) of proteins, which sense pathogens and pathogen products in the cell cytoplasm [1]. The NLR family of proteins has been increasingly associated with various aspects of innate and adaptive immune system regulation, inflammation, and autoimmunity. The majority of NLR studies have focused on a subgroup of NLR family members that are capable of forming a multiprotein complex, termed the inflammasome, with the NLR adaptor protein PYCARD (ASC) and Caspase-1. In addition to the inflammasome forming NLRs, recent studies have revealed a second subgroup of NLRs that have anti-inflammatory functions, which dampen overzealous immune responses. The members of this subgroup include NLRP12, NLRX1, NLRC3 and NLRC5 [3,4,5,6,7]. While the overwhelming majority of studies have focused on the role of the NLRs in mediating the host innate immune response, several recent studies have suggested that select NLRs may participate in the initiation of the adaptive immune response
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