Crucial roles of macrophages in the pathogenesis of autoimmune disease

Figure 1 Macrophage differentiation and resident macrophages. A: Naïve monocytes differentiate into M1, M2 and atherosclerosis-related macrophages [M(Hb), Mox, and M4] by various stimuli. M1 macrophages enhance inflammation through producing TNF-α, IL-1β, IL-6, IL-12 and IL-23. M2 macrophages polarize to three subsets (M2a, M2b and M2c) by cytokines or ICs to suppress inflammation and repairs tissues through producing regulatory cytokines, such as IL-10, TGF-β, Il-1R ligands and IL-6. Macrophage precursors (monocytes) are circulating, and quickly migrate into all tissues of the body, in which monocytes differentiate into mature macrophages with unique functions in each tissue; B: Resident /tissue macrophages are derived from bone marrow, yolk sac, and fetal liver to settle in various tissues. Resident macrophages contribute to homeostasis in the tissues. OxPLs: Oxidized phospholipids; ICs: Immune complexes; IFN: Interferon; TNF: Tumor necrosis factor; IL: Interleukin; MCP-1: Monocyte chemotactic protein-1; LPS: Lipopolysaccharide; iNOS: Inducible nitric oxide synthase.

Figure 2 Macrophages in autoimmune lesions. CD68⁺ macrophages infiltrate in the salivary gland tissue from SS patients. Immunohistochemical analysis using paraffin-embedded sections from lip biopsy materials was performed by staining with anti-CD68 antibody (DAKO). Biotinylated antibody and horseradish peroxidase (HRP)-conjugated streptavidin (LSAB kit, DAKO) was used as a secondary antibody, and then CD68⁺ cells were detected by using 3,3’-Diaminobenzidine (DAB) as a substrate. Counter staining was performed with hematoxylin. Original magnificaion is × 400. Arrows show CD68⁺ macrophages.