NLRP10 Enhances CD4⁺ T-Cell-Mediated IFNγ Response via Regulation of Dendritic Cell-Derived IL-12 Release

NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a Nlrp10 mouse to delineate the role of NLRP10 in the host immune response and found that Nlrp10 dendritic cells (DCs) elicited sub-optimal IFNγ production by antigen-specific CD4⁺ T cells compared to wild-type (WT) DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, Nlrp10 DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident in vivo and affected IFNγ production by CD4⁺ T cells. Upon Mycobacterium tuberculosis (Mtb) infection, Nlrp10 mice displayed diminished T helper 1-cell responses and increased bacterial growth compared to WT mice. These data indicate that NLRP10-mediated IL-12 production by DCs is critical for IFNγ induction in T cells and contributes to promote the host defense against Mtb.