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Fig. 7 | Journal of Neuroinflammation

Fig. 7

From: The spleen may be an important target of stem cell therapy for stroke

Fig. 7

Effects of MSCs on various immune cells in circulation and in the spleen after stroke. a MSCs affect various immune cells in circulation and the spleen after stroke through soluble molecules and direct interactions [198,199,200]. b T cell activation triggers the expansion of T cell clones and secretion of TNF-α and other inflammatory factors. Then, TNF-α activates the NF-κB signalling pathway in MSCs located in inflammatory environments through the TNF receptor, thereby inducing MSC-mediated immunosuppression [194, 201, 202]. c Similar to T lymphocytes, TNF-α produced by activation of the NF-κB signalling pathway in macrophages also induces MSC-mediated immunosuppression, which inhibits macrophage activation and converts macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype by blockade of NF-κB. During this process, NF-κB signal activation in MSCs upregulates COX2 expression, which is turn increases the synthesis of prostaglandin E2 (PGE2). The secreted PGE2 binds to EP2 and EP4 receptors on macrophages, thereby increasing IL-10 secretion by macrophages to reduce inflammation [203, 204]

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