**Acknowledgements**

*Cells of the Immune System*

**4. Immunomodulation of macrophages in the immune system**

and IL-6, to promote macrophage activity [75–78].

rides may effectively regulate cellular immune response [84].

**5. Immunomodulation of macrophage differentiation**

angiogenesis-promoting growth factors.

Polysaccharides extracted from mushrooms or algae have immunomodulatory functions, such as increasing macrophage activity, regardless of whether innate or adaptive immunity is activated [64]. For instance, the phagocytic activity of cells, the killing ability of natural killer cells, and the promotion of immune cells to secrete cytokines activate the immune system. In our previous laboratory studies, mushroom polysaccharide administration could enhance the tumour-suppressive and antiallergic ability in mice, along with significant enhancement in the woundhealing ability in rats. Immune cells of the innate immune response, such as macrophages and dendritic cells, or other nonimmune cells, such as epithelial cells, have many nonspecific recognition receptors associated with antigens that evade pathogens. Based on molecular identification and binding, complement receptor type 3 (CR3) on these cells can identify polysaccharides [65]. When polysaccharides bind to CR3, it triggers a series of signalling to activate transcription factors. Cells secrete a cytokine that triggers an inflammatory response, and the antigen exhibits the major histocompatibility complex of the cell, thereby activating other immune cells to achieve immunomodulatory functions [66, 67]. Dectin-1 belongs to the c-type lectin receptor family and is expressed on the cell membranes of macrophages, dendritic cells, neutrophils, and T and B cells [68]. Dectin-1 binds to polysaccharides to promote macrophage phagocytosis and respiratory burst; it also promotes the degranulation of neutrophils and secretion of cytokines and chemokines from immune cells [69–72]. Polysaccharides from *Antrodia camphorata* were cocultured with immature dendritic and T cells isolated from healthy human blood, and the polysaccharides could promote dendritic cell maturation and stimulate T-cell proliferation and IFN-γ performance [73, 74]. Coculture of polysaccharides with macrophages can promote the secretion of immune-related factors and cytokine gene expression, such as nitric oxide (NO), tumour necrosis factor (TNF)-α, IL-1β,

Based on our teams' experimental results, the functional polysaccharide can stimulate macrophages and further activate cytokines TNF-α, IL-12, IFN-γ, IL-2, IL-4, IL-10, and IL-17, which are associated with apoptosis and cell cycle. Growth hormone, a multipeptide hormone regulator, promotes growth and cell proliferation [75, 78, 79]. Polysaccharides can reduce CCl4-induced liver damage by regulating related antioxidant enzymes and effectively reducing oxidative damage in liver tissue [80, 81]. In mice, intraperitoneal polysaccharide injection could effectively prevent lipid peroxidation and inhibit the production of reactive oxygen species in the liver [82, 83]. Taken together, the immunomodulation function of polysaccha-

Immune cells are crucial in immune response modulation. As mentioned, macrophages polarise into M1 and M2 macrophages, which have distinct functions and are affected by the physiological microenvironment factors. M1 macrophages perform pathogen elimination through phagocytosis, inflict oxidative damage, and complement system activation. M2 macrophages have tissue recovery functions. Tumour tissues contain considerable amounts of M2 macrophages that release

Inflammatory reactions can induce chronic diseases; thus, reducing inflammation is important for inhibiting chronic disease. To achieve anti-inflammatory effects, immunotherapy is a novel therapeutic approach without known side effects

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This project was supported by the Ministry of Science and Technology, Taiwan (MOST. 107-2313-B-020-004).
