Alternatively activated myeloid (M2) cells enhance cognitive function in immune compromised mice

Graduate Program in Neuroscience, Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA.
Brain Behavior and Immunity (Impact Factor: 5.89). 03/2011; 25(3):379-85. DOI: 10.1016/j.bbi.2010.11.009
Source: PubMed


It was recently shown that adaptive immunity plays a key role in cognitive function. T cells appear to be major players in learning and memory; thus, mice devoid of functional T cells are impaired in performance of cognitive tasks such as Morris water maze (MWM), Barnes maze and others. This is a reversible phenomenon; injection of immune deficient mice with T cells from wild type counterparts improves their cognitive function. Recently we described a critical role for T cell-derived IL-4 as having beneficial effects on learning and memory through regulation of meningeal myeloid cell phenotype. In the absence of IL-4, meningeal myeloid cells acquire a pro-inflammatory skew. Thus, the presence of IL-4 in the meningeal spaces maintains a delicate balance of pro- and anti-inflammatory myeloid cell phenotype. Here we show that macrophages alternatively activated in vitro (M2 cells) can circumvent the need for 'pro-cognitive' T cells when injected intravenously into immune deficient mice. These results show for the first time that M2 myeloid cells are new and unexpected players in cognitive function, conferring beneficial effects on learning and memory without adaptive immune influence. These results might lead to development of new therapeutic approaches for cognitive pathologies associated with malfunction of adaptive immunity, such as chemo-brain, age-related dementia, HIV-dementia, and others.

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Available from: Noel Derecki, Dec 03, 2014
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    • "Mice that lack IL-4 demonstrated cognitive impairment in spatial learning tasks; after transplantation with IL-4 competent bone marrow, this impairment was reversed [34]. A proposed mechanism by which IL-4 promotes cognition is that it exerts its effect through an anti-inflammatory M2-skew of meningeal macrophages, which has been shown to be both beneficial after CNS injury [35] and required for learning [36]. These findings support the concept that a pro-inflammatory state can be detrimental to the developing brain and suggest a potential role for IL-4 in tissue repair and neuroprotection. "
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    • "The authors were the first to describe a critical role for T cell derived IL-4 as key cytokine involved in learning and memory through regulation of myeloid cells present in the meningeal space (32, 57). This intriguing new concept has been recently confirmed by showing improved learning and memory in T cell deficient SCID mice adoptively transferred with M2 macrophages (58). Considering the well-known crosstalk between cognition and emotion regulation (31), it would be interesting to explore the possible changes in myeloid cell phenotype during the early stages of the EAE. "
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    • "These neurobiological functions are thought to contribute to blood-derived macrophages support of learning and memory (as determined via the Morris Water Maze and Barnes Maze; Derecki et al., 2010, 2011). Importantly, intravenous injection of M2 cells into immune-deficient mice can circumvent the need for CNS-specific autoreactive CD4+ T cells (Derecki et al., 2011). For a review of the role of blood-derived macrophages see recent papers (Derecki et al., 2010; Martino et al., 2011; Yirmiya and Goshen, 2011). "
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