Arginase-2 is Essential for IL-10 Metabolic Reprogramming of Inflammatory Macrophages at the Mitochondria

Adjuvant and immunomodulatory potential ofin vivoNatural Killer T (NKT) activation by NKTT320

“…As illustrated in the schematic (Figure 12), side-by-side with activation, NKTT320 triggered several genes encoding markers of resolution of inflammation. Most prominent of the upregulated genes included the inflammation resolution genes NLRP12 and CMKLR1 (48,70), the metabolic regulator ARG-2 (46), and the inhibitory receptors FCGR2B and PD-L1 (33,42). In all, the concordant immune activation and anti-inflammatory responses induced by NKTT320 may mean that there is a potential in vivo for eliciting potent inflammatory responses without excessive or non-resolving immune activation.…”

“…Simultaneously an immune downmodulation effect of NKTT320 was evident by upregulation of several immune inhibitory and inflammation suppressive genes (Figure 8). These included the T-lymphocyte inhibitor PD-1 ligand 1 (CD274) (42); the arginine metabolism enzyme ARG2 that can regulate inflammation and immunity (43)(44)(45)(46); the potent mitigator of inflammation, nucleotide-binding oligomerization domain protein NLRP12 that acts as a negative regulator of NF-B and promotes degradation of NOD (47); the chemerin chemokine-like receptor CMKLR1 which binds the endogenous lipid mediator Resolvin E1 and actively regulates resolution of acute inflammation (48), the suppressor of cytokine signaling SOCS3 involved in the negative regulation of cytokines such as IL6 that signal through the JAK/STAT pathway (49), and ROR1 that can inhibit the Wnt3a-mediated signaling pathway (50). These data point to an inflammation suppressive effect of NKTT320-mediated iNKT activation acting in concert with activation of B-cells, monocytes, dendritic cells, and T-helper pathways.…”