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

Proc Natl Acad Sci U S A. 2017 Aug 8;114(32):8620-8625. doi: 10.1073/pnas.1700917114. Epub 2017 Jul 24.


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 (Car6-b, which encoded CA-VI B) is essential for host defense against Listeria monocytogenes (LM) infection by epigenetically promoting IL-12 expression independent of its carbonic anhydrase activity. Deficiency of Car6-b attenuated IL-12 production upon LM infection both in vitro and in vivo. Car6-/- 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 N-methyltransferase 5 (PRMT5), which reduces symmetric dimethylation of histone H3 arginine 8 modification (H3R8me2s) at Il12 promoters to facilitate chromatin accessibility, selectively enhancing c-Rel binding to the Il12b promoter. Our findings add insights to the epigenetic regulation of IL-12 induction in innate immunity.

Keywords: Car6-b; IL-12; PRMT5; epigenetic modification; innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Carbonic Anhydrases / genetics
  • Carbonic Anhydrases / immunology*
  • Cell Nucleus / genetics
  • Cell Nucleus / immunology*
  • Epigenesis, Genetic / immunology*
  • Histones / genetics
  • Histones / immunology
  • Immunity, Innate*
  • Interleukin-12 Subunit p40 / genetics
  • Interleukin-12 Subunit p40 / immunology*
  • Listeria monocytogenes / immunology
  • Listeriosis / genetics
  • Listeriosis / immunology
  • Methylation
  • Mice
  • Mice, Knockout
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / immunology*


  • Histones
  • Interleukin-12 Subunit p40
  • Prmt5 protein, mouse
  • Protein-Arginine N-Methyltransferases
  • Carbonic Anhydrases
  • carbonic anhydrase VI