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

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

Xu J1, Xu X1, Wang B1, Ma Y2, Zhang L2, Xu H1, Hu Y1, Wu J1, Cao X3,4.

Author information

1
Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China.
2
Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100021, China.
3
Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China; caoxt@immunol.org.
4
National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, Shanghai 200433, China.

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 (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

PMID:
28739930
PMCID:
PMC5559001
DOI:
10.1073/pnas.1700917114
[Indexed for MEDLINE]
Free PMC Article

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