NLRP10 ENHANCES THE TH1 IMMUNE RESPONSE VIA REGULATION OF DENDRITIC CELL-MEDIATED IL-12 RELEASE

Abstract

The NLRs are a class of intracellular PRRs. NLRP10 is a member with unique features of this family, as it is the only NLR without LRR domain. NLRP10 is poorly characterized and its biological role unknown. In this study we generated an Nlrp10-/- mouse to define the functions of NLRP10 in the immune response. Results showed that Nlrp10-/- dendritic cells (DCs) elicited sub-optimal IFNγ production by antigen-specific CD4+ T cells compared to WT. Specifically, in response to T-cell encounter, CD40 ligation or r TLR9 stimulation, Nlrp10-/- DCs produced low levels of IL-12, caused by an impairment in NF-κB signalling cascade compared to WT. Defective IL-12 production was also evident in vivo and affected IFNγ production by CD4+ T cells. These data indicate that NLRP10-mediated IL-12 production by DCs is critical for IFNγ induction in T cells and promotes the host defence against intracellular bacterial pathogens, moreover these data assign for the first time a role to NLRP10 as fine regulator of adaptive immune response.