Frontiers in Immunology (Nov 2019)
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
- Bin Lai,
- Bin Lai,
- Jiwei Wang,
- Jiwei Wang,
- Alexander Fagenson,
- Alexander Fagenson,
- Yu Sun,
- Jason Saredy,
- Yifan Lu,
- Gayani Nanayakkara,
- William Y. Yang,
- Daohai Yu,
- Ying Shao,
- Charles Drummer,
- Candice Johnson,
- Fatma Saaoud,
- Ruijing Zhang,
- Qian Yang,
- Keman Xu,
- Kevin Mastascusa,
- Ramon Cueto,
- Hangfei Fu,
- Susu Wu,
- Lizhe Sun,
- Peiqian Zhu,
- Xuebin Qin,
- Xuebin Qin,
- Jun Yu,
- Daping Fan,
- Ying H. Shen,
- Ying H. Shen,
- Jianxin Sun,
- Thomas Rogers,
- Eric T. Choi,
- Eric T. Choi,
- Eric T. Choi,
- Hong Wang,
- Xiaofeng Yang,
- Xiaofeng Yang
Affiliations
- Bin Lai
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Bin Lai
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Jiwei Wang
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Jiwei Wang
- Department of Ultrasound, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Alexander Fagenson
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Alexander Fagenson
- Division of Abdominal Organ Transplantation, Department of Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Yu Sun
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Jason Saredy
- Metabolic Disease Research, Cardiovascular Research, & Thrombosis Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Yifan Lu
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Gayani Nanayakkara
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- William Y. Yang
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Daohai Yu
- Department of Clinical Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Ying Shao
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Charles Drummer
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Candice Johnson
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Fatma Saaoud
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Ruijing Zhang
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Qian Yang
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Keman Xu
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Kevin Mastascusa
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Ramon Cueto
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Hangfei Fu
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Susu Wu
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Lizhe Sun
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Peiqian Zhu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Xuebin Qin
- Division of Vascular and Endovascular Surgery, Department of Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Xuebin Qin
- Tulane National Primate Research Center, School of Medicine, Tulane University, Covington, LA, United States
- Jun Yu
- Metabolic Disease Research, Cardiovascular Research, & Thrombosis Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Daping Fan
- Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, United States
- Ying H. Shen
- 0Cardiothoracic Surgery Research Laboratory, Texas Heart Institute, Houston, TX, United States
- Ying H. Shen
- 1Department of Surgery, Baylor College of Medicine, Houston, TX, United States
- Jianxin Sun
- 2Center for Translational Medicine, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States
- Thomas Rogers
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Eric T. Choi
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Eric T. Choi
- Division of Vascular and Endovascular Surgery, Department of Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Eric T. Choi
- Tulane National Primate Research Center, School of Medicine, Tulane University, Covington, LA, United States
- Hong Wang
- Metabolic Disease Research, Cardiovascular Research, & Thrombosis Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Xiaofeng Yang
- Centers for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- Xiaofeng Yang
- Metabolic Disease Research, Cardiovascular Research, & Thrombosis Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
- DOI
- https://doi.org/10.3389/fimmu.2019.02612
- Journal volume & issue
-
Vol. 10
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.
Keywords
- macrophages
- disease-specific and shared pathways
- immune checkpoint receptors
- trained immunity
- immunometabolism pathways
