Table 2 Role of tissue macrophages in diseases
From: Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets
Disease Category | Specific Diseases | Macrophage Subtypes | Secretory Phenotype | Biological Function | References |
|---|---|---|---|---|---|
Cancer | tumor microenvironment | M1 macrophages (CD14, CD16/CD33, CD40, CD86, CD80, iNOS, and TLR2) | IL-1α, IL-1β, IL-6, IL-12, IL-23, CXCL9, CXCL10, CCL5, COX-2, and TNF-α | Phagocytosis of tumor cells, enhancing the function of antigen presentation, and releasing inflammatory cytokines to activate the anti-tumor efficacy of adaptive immunity | |
M2 macrophages (M2a: CD206, CD163, and Arg-1; M2b: CD86, HLA-DR; M2c: CD163, CD206, and MerTK; M2d: TLR2, TLR4, TLR7, and TLR9) | IL-10, IL-4, TGF-β, Arg-1, PGE2, VEGF, MMPs, IDO, and glucocorticoids | Promoting tumor growth, remodeling the tumor metabolic immune microenvironment, enhancing its invasiveness and metastasis, angiogenesis, and immune evasion | |||
Tie2+ TAMs | VEGF, PDGF-β, and CECR1 | Promoting the development and maturation of tumor vasculature | |||
SPP1+ TAMs | MMP9, MMP12, MMP14, MMP19, VEGF-A, collagen, IGF-1 | Promoting angiogenesis and tumor growth | |||
C1Q+ TAMs | IL-10, IDO | Promoting Treg recruitment, inhibiting the effector function of CD8 T cells, and promoting M2 macrophage polarization | |||
FCN1+ TAMs | Not clarified | Related to tumor-associated inflammatory functions | |||
CCL18+ TAMs | CCL18 | Promoting tumor proliferation and shaping the tumor immunosuppressive microenvironment | |||
glioblastoma | CD11b+ CD163+ TAMs | PTN | Promoting the growth and development of glioblastoma | ||
TIM3+ VISTA+ TAMs | Not clarified | hindering the production of pro-inflammatory TAMs | |||
Hypoxia-TAMs | ADM | Promoting tumor vascular instability, affecting the efficacy of anti-tumor drugs | |||
CD68+ SOX2+ TAMs | Not clarified | Shaping the immune microenvironment leads to resistance to ICB therapy | |||
Breast cancer | Lyve-1+ TAMs | PDGF-C | Expanding the perivascular stromal cell population to create an environment conducive to angiogenesis | ||
APOE+ TAMs | Not clarified | Promoting CD8+ T cell exhaustion | |||
STAB1+ TREM2+ TAMs | Not clarified | Shaping the immunosuppressive microenvironment | |||
Ependymoma | CCL2+ TAMs | IL-1β, CCL3, CCL4 | Promoting inflammatory responses to inhibit tumor occurrence and development | ||
CD44+ TAMs | VEGFA | Promoting tumor angiogenesis | Â | ||
Inflammation and autoimmune disease | Rheumatoid arthritis (RA) | CX3CR1hi Ly6Clow F4/80low IA/IElow Macrophages (arthritis-associated osteoclastogenic macrophages) | IL-6, TNF-α | Promoting RA joint destruction | |
CD11b+ Flt-1+ GRK2+ macrophages | VEGF | Promoting synovitis and angiogenesis | |||
Systemic lupus erythematosus (SLE) | CD40L+ Macrophages (M1) | IL-1β, IFN-γ, CXCL10, CCL2, IL-6, and TNF-α | Activating B cells, promoting antibody production, and exacerbating systemic inflammatory responses | ||
Systemic sclerosis (SSc) | CD163+ Macrophages (M2) | TGF-β, PDGF, and CCL18 | Promoting skin and lung fibrosis | ||
SPP1+ Macrophages | TGF-β, PDGF |  | |||
FCGR3A+ Macrophages | IL-6, CCL18 | Â | |||
CD163+ CXCL10+ Fli- (Mixed M1/M2 phenotype) Macrophages | M1 and M2-associated cytokines | Â | |||
Cardiovascular diseases | Myocardial Infarction (MI) | Ly-6C− MHC-IIhi CX3CR1hi CD206int MerTK+ CD11clow CCR2− CD64+ Macrophages | Not clarified | Phagocytosis and immune surveillance | |
Ly-6C− MHC-IIhi CX3CR1hi CD206int MerTK+ CD11chi CCR2+ CD103− CD64+ | TNF-α, IL-1, IL-6, MCP-1, and MMPs | Clearing damaged tissue but also potentially exacerbating myocardial remodeling and fibrosis |  | ||
Ly-6C− Nr4a1+ CD206+ MerTK+ Macrophages | IL-10, TGF-β, HIF-α, VEGFA, and SPP1 | Promoting tissue repair and healing as well as fibrosis | |||
Bhlhe41+ Macrophages | Not clarified | Preventing excessive myocardial fibrosis and promoting repair | |||
Atherosclerosis (AS) | CCR2+ Macrophages (M1) | IL-1β, IL-6, TNF-α, MMP1, MMP3, and MMP10 | Promoting the progression of atherosclerosis and causing plaque instabilit | ||
CCR2- Macrophages (M2) | IL-10, TGF-β, MMP11, MMP12, MMP15 | Suppressing inflammation and promoting cholesterol efflux |  | ||
SR-A+ CD36+ LOX-1+ Macrophages (LAMs) | IL-1β, IL-6, TNF-α, and MMPs | Forming plaques and promoting their instability and necrosis | |||
Neurodegeneration disease | Alzheimer’s disease | SPP1+ TREM2+ DAMs | SPP1 | Participating in the phagocytosis of amyloid-beta and involved in activating immune regulatory pathways | |
CD36+ BAMs | ROS | Causing neurovascular dysfunction, cerebral amyloid angiopathy (CAA), and cognitive impairment | |||
CD169+ DIMs | TIMP1, MMP9 | Increasing inflammatory responses and extracellular matrix remodeling | |||
Parkinson’s Disease | CD11b+ TMEM119+ LRRK2+ Microglia | Not clarified | Exacerbating neuroinflammatory responses and neurotoxicity | ||
CD68+ MHC-II Microglia | TNF-α, IL-1β | Promoting antigen presentation and T cell activation | |||
Metabolic disorders | Non-Alcoholic Fatty Liver Disease (NAFLD) | CD36+ PLIN2+ ABCA1+ TREM2+ Macrophages (ATMs) | Not clarified | Possessing strong capabilities in fat uptake and metabolism | |
TIM4+ VSIG4+ CLE4F+ FOLR2+ Macrophages (KCs) | IL-1β, ΤNF-α | Inhibiting the PPARα pathway in hepatocytes, thereby impairing lipid metabolism and exacerbating hepatic steatosis | |||
TIM4- Ly-6Chi CCR2+ Macrophages (MoKCs) | IL-1β, ΤNF-α |  | |||
TREM2+ Macrophages (LAMs) | IL-1β, ΤNF-α |  | |||
SPP1+ LGALS3+ CCR+ TNFSF12+ Macrophages | TGF-β, TNF, IL-1β, and galectin-3 | Promoting liver fibrosis and leading to cirrhosis | |||
TREM2+ GPNMB+ SLC40A1+ APOE+ C1QA+ Macrophages (TAMs) | TNF-α, IL-6, TGF-β, and MCP-1 | Shaping an immunosuppressive microenvironment in liver cancer, promoting angiogenesis, and liver cancer growth | |||
Trauma | Wound microenvironment | CD206+ Macrophages (M2a) | TGF-β, VEGF | Promoting wound angiogenesis and scar tissue formation | |
CD163+ CD206+ MerTK+ Macrophages (Mreg) | TGF-β | Phagocytosing excessive matrix to prevent fibrosis | |||
Traumatic spinal cord injury | TMEM119+ Macrophages | IL-1β, IL-6, TNF-α | Causing persistent inflammation around the lesion and damage to neuronal axons and dendrites | ||
MRC1+ Macrophages | IL-10 | Reducing the formation of microglia and astrocytes in neural injury |
