====== M2 macrophage ======


Beyond increasing inflammation and stimulating the immune system, [[macrophage]]s also play an important anti-inflammatory role and can decrease immune reactions through the release of [[cytokine]]s. Macrophages that encourage inflammation are called [[M1 macrophage]]s, whereas those that decrease inflammation and encourage tissue repair are called [[M2 macrophage]]s.
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M2-type [[macrophage]]s, also known as alternatively activated macrophages, are a type of immune cell that plays an important role in tissue repair, remodeling, and immunoregulation. M2-type macrophages are polarized in response to specific stimuli, such as interleukin-4 (IL-4) or interleukin-13 (IL-13), and are characterized by the expression of specific markers, such as CD206 (mannose receptor), arginase-1 (Arg1), and chitinase-like proteins.

M2-type macrophages are involved in a variety of physiological and pathological processes, including wound healing, tissue regeneration, allergic reactions, and parasite infections. M2-type macrophages promote tissue repair and regeneration by secreting growth factors and extracellular matrix proteins, as well as by phagocytosing apoptotic cells and debris.

M2-type macrophages are also involved in immunoregulation, as they can suppress inflammation and promote tissue tolerance. M2-type macrophages can inhibit the activation of pro-inflammatory immune cells, such as T cells and natural killer cells, and can also secrete anti-inflammatory cytokines, such as IL-10 and transforming growth factor-beta (TGF-β).

The dysregulation of M2-type macrophages has been implicated in the pathogenesis of various diseases, including cancer, fibrosis, and chronic infections. Understanding the molecular mechanisms that regulate M2-type macrophage polarization and function is important for developing new therapies for these diseases.
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exosomes derived from M2-polarized macrophages (M2-Exo) in ischemic stroke have not yet been reported. In this study, we established an in vitro oxygen/glucose deprivation and re-oxygen/glucose (OGD/R) model to investigate the potential role of M2-Exo in protecting HT22 neurons against ischemia-reperfusion injury. Interleukin-4 was used to induce the M2 phenotype in macrophages, following which the exosomes were isolated from the supernatant of M2-polarized macrophages and identified by western blotting, transmission electron microscopy, and nanoparticle tracking analysis. After co-incubation with M2-Exo, OGD/R-induced neuronal injury in HT22 cells was improved, accompanied by increased cell viability and decreased lactate dehydrogenase release. In addition, the increase in the percentage of terminal deoxyribonucleotide transferase-mediated dUTP-digoxigenin nick-end labeling-positive cells in OGD/R-treated HT22 cells was attenuated after incubation with M2-Exo. M2-Exo treatment also suppressed reactive oxygen species and malondialdehyde production and improved the reduction of superoxide dismutase activity. Moreover, M2-Exo treatment was found to activate the nuclear factor erythroid related factor 2 (Nrf2)/heme-oxygenase-1 (HO-1) signaling pathway in OGD/R-treated HT22 neurons. Importantly, inhibition of Nrf2 by ML385 partially reversed the protective effects of M2-Exo against OGD/R-induced oxidative damage. Taken together, these data demonstrated that M2-Exo exerted protective effects against OGD/R-induced oxidative damage in HT22 neurons, which was mediated by the activation of Nrf2/HO-1 signaling. Hence, our findings provide a promising therapeutic approach for ischemic stroke
((Xiao T, Qu H, Zeng Z, Li C, Wan J. Exosomes from M2-polarized macrophages relieve oxygen/glucose deprivation/normalization-induced neuronal injury by activating the Nrf2/HO-1 signaling. Arch Biochem Biophys. 2022 Mar 20:109193. doi: 10.1016/j.abb.2022.109193. Epub ahead of print. PMID: 35321825.)).