Nuclear carbonic anhydrase 6B associates with PRMT5 to epigenetically promote IL-12 expression in innate response.

Abstract

Interleukin-12 (IL-12) is critical for induction of protective immunity against intracellular bacterial infection. However, the mechanisms for efficient induction of IL-12 in innate response remain poorly understood. Here we report that the B type of carbonic anhydrase 6 (<i>Car6-b</i>, which encoded CA-VI B) is essential for host defense against <i>Listeria monocytogenes</i> (LM) infection by epigenetically promoting IL-12 expression independent of its carbonic anhydrase activity. Deficiency of <i>Car6-b</i> attenuated IL-12 production upon LM infection both in vitro and in vivo. <i>Car6</i>^-/- mice were more susceptible to LM infection with less production of IL-12. Mechanistically, the nuclear localized CA-VI B selectively promotes IL-12 expression by interaction with protein arginine <i>N</i>-methyltransferase 5 (PRMT5), which reduces symmetric dimethylation of histone H3 arginine 8 modification (H3R8me2s) at <i>Il12</i> promoters to facilitate chromatin accessibility, selectively enhancing c-Rel binding to the <i>Il12b</i> promoter. Our findings add insights to the epigenetic regulation of IL-12 induction in innate immunity.