PTIP governs NAD+ metabolism by regulating CD38 expression to drive macrophage inflammation.

Cell reports 2022 Mar 29

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NAD+ metabolism is involved in many biological processes. However, the underlying mechanism of how NAD+ metabolism is regulated remains elusive. Here, we find that PTIP governs NAD+ metabolism in macrophages by regulating CD38 expression and is required for macrophage inflammation. Through integrating histone modifications with NAD+ metabolic gene expression profiling, we identify PTIP as a key factor in regulating CD38 expression, the primary NAD+-consuming enzyme in macrophages. Interestingly, we find that PTIP deletion impairs the proinflammatory response of primary murine and human macrophages, promotes their metabolic switch from glycolysis to oxidative phosphorylation, and alters NAD+ metabolism via downregulating CD38 expression. Mechanistically, an intronic enhancer of CD38 is identified. PTIP regulates CD38 expression by cooperating with acetyltransferase p300 in establishing the CD38 active enhancer with enriched H3K27ac. Overall, our findings reveal a critical role for PTIP in fine-tuning the inflammatory responses of macrophages via regulating NAD+ metabolism. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Qifan Wang, Jin Hu, Guoqiang Han, Peipei Wang, Sha Li, Jiwei Chang, Kexin Gao, Rong Yin, Yashu Li, Tong Zhang, Jihua Chai, Zhuying Gao, Tiantian Zhang, Ying Cheng, Chengli Guo, Jing Wang, Weidong Liu, Manman Cui, Yu Xu, Jinxuan Hou, Quan-Fei Zhu, Yu-Qi Feng, Haojian Zhang. PTIP governs NAD+ metabolism by regulating CD38 expression to drive macrophage inflammation. Cell reports. 2022 Mar 29;38(13):110603