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Lai B , Wang J , Fagenson A , Sun Y , Saredy J , Lu Y , Nanayakkara G , Yang WY , Yu D , Shao Y , Drummer Cth , Johnson C , Saaoud F , Zhang R , Yang Q , Xu K , Mastascusa K , Cueto R , Fu H , Wu S , Sun L , Zhu P , Qin X , Yu J , Fan D , Shen YH , Sun J , Rogers T , Choi ET , Wang H , Yang X
Twenty Novel Disease Group-Specific and 12 New Shared Macrophage Pathways in Eight Groups of 34 Diseases Including 24 Inflammatory Organ Diseases and 10 Types of Tumors
Front Immunol. 2019 ;10 :2612
PMID: 31824480    PMCID: PMC6880770    URL: https://www.ncbi.nlm.nih.gov/pubmed/31824480
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Abstract
The mechanisms underlying pathophysiological regulation of tissue macrophage (Mφ) subsets remain poorly understood. From the expression of 207 Mφ genes comprising 31 markers for 10 subsets, 45 transcription factors (TFs), 56 immunometabolism enzymes, 23 trained immunity (innate immune memory) enzymes, and 52 other genes in microarray data, we made the following findings. (1) When 34 inflammation diseases and tumor types were grouped into eight categories, there was differential expression of the 31 Mφ markers and 45 Mφ TFs, highlighted by 12 shared and 20 group-specific disease pathways. (2) Mφ in lung, liver, spleen, and intestine (LLSI-Mφ) express higher M1 Mφ markers than lean adipose tissue Mφ (ATMφ) physiologically. (3) Pro-adipogenic TFs C/EBPα and PPARγ and proinflammatory adipokine leptin upregulate the expression of M1 Mφ markers. (4) Among 10 immune checkpoint receptors (ICRs), LLSI-Mφ and bone marrow (BM) Mφ express higher levels of CD274 (PDL-1) than ATMφ, presumably to counteract the M1 dominant status via its reverse signaling behavior. (5) Among 24 intercellular communication exosome mediators, LLSI- and BM- Mφ prefer to use RAB27A and STX3 than RAB31 and YKT6, suggesting new inflammatory exosome mediators for propagating inflammation. (6) Mφ in peritoneal tissue and LLSI-Mφ upregulate higher levels of immunometabolism enzymes than does ATMφ. (7) Mφ from peritoneum and LLSI-Mφ upregulate more trained immunity enzyme genes than does ATMφ. Our results suggest that multiple new mechanisms including the cell surface, intracellular immunometabolism, trained immunity, and TFs may be responsible for disease group-specific and shared pathways. Our findings have provided novel insights on the pathophysiological regulation of tissue Mφ, the disease group-specific and shared pathways of Mφ, and novel therapeutic targets for cancers and inflammations.
Notes
1664-3224 Lai, Bin Wang, Jiwei Fagenson, Alexander Sun, Yu Saredy, Jason Lu, Yifan Nanayakkara, Gayani Yang, William Y Yu, Daohai Shao, Ying Drummer, Charles 4th Johnson, Candice Saaoud, Fatma Zhang, Ruijing Yang, Qian Xu, Keman Mastascusa, Kevin Cueto, Ramon Fu, Hangfei Wu, Susu Sun, Lizhe Zhu, Peiqian Qin, Xuebin Yu, Jun Fan, Daping Shen, Ying H Sun, Jianxin Rogers, Thomas Choi, Eric T Wang, Hong Yang, Xiaofeng R01 HL138749/HL/NHLBI NIH HHS/United States R01 HL130233/HL/NHLBI NIH HHS/United States R01 HL131460/HL/NHLBI NIH HHS/United States R01 DK104116/DK/NIDDK NIH HHS/United States R01 HL132399/HL/NHLBI NIH HHS/United States R01 HL147565/HL/NHLBI NIH HHS/United States R01 DK113775/DK/NIDDK NIH HHS/United States R01 HL117654/HL/NHLBI NIH HHS/United States P51 OD011104/OD/NIH HHS/United States Journal Article Research Support, Non-U.S. Gov't Front Immunol. 2019 Nov 14;10:2612. doi: 10.3389/fimmu.2019.02612. eCollection 2019.