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: 6.13). 03/2011; 25(3):379-85. DOI: 10.1016/j.bbi.2010.11.009
Source: PubMed

ABSTRACT 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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    • "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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    Frontiers in Psychiatry 02/2013; 4:3. DOI:10.3389/fpsyt.2013.00003
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    • " to depression , i . e . neurogenesis and cytokine regulation , include T regs , CD4+ T cells , mono - cyte - derived macrophages , astrocytes and microglia ( Moa - lem et al . , 1999 ; Schwartz and Kipnis , 2002 ; Cohen et al . , 2006 ; Ishibashi et al . , 2009 ; Liu et al . , 2009 ; Schwartz and Shechter , 2010a , b ; Capuron and Miller , 2011 ; Derecki et al . , 2011 ) . The specific role of these cells in the neuroimmune— neurogenesis communication in physiological and pathophys - iological conditions will be outlined below ."
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    Psychoneuroendocrinology 04/2012; 37(9):1397-416. DOI:10.1016/j.psyneuen.2012.03.019 · 5.59 Impact Factor
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    • "In addition , although it was suggested that IL-4 may drive alternative activation of meningeal macrophages, this was not demonstrated using the same criteria used by Nguyen et al. (2011). However, later studies showed that the cognitive defects in SCID mice uncovered by this model were partially ameliorated by provision of in vitro–generated AAM (Derecki et al., 2011). If cognition drives the accumulation of functionally important IL-4–secreting lymphocytes to the meninges , this would provide a potential novel mechanism behind the " use it or lose it " admonition in terms of salvaging cognition from the ravages of aging, a state in which there are likely multiple causes for pernicious up-regulation of proinflammatory cytokine production in the central nervous system. "
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