CD4 + CD25 + regulatory T cells (Treg cells) are important in maintenance of peripheral tolerance. The direct effect of CD4 + CD25 + Treg cells on macrophages was studied using a mouse model in which syngeneic CD4 + CD25 + Treg cells were adoptively transferred into the peritoneal cavity of SCID mice. Peritoneal macrophages in mice transferred with CD4 + CD25 + Treg cells expressed significantly higher levels of CD23, CD47 and CD206 and less CD80 and major histocompatibility complex class II molecules as compared with those mice that received either CD4 + CD25 À T cells or no cells. Macrophages of mice injected with CD4 + CD25 + Treg cells displayed a remarkably enhanced phagocytosis of chicken red blood cells, and arginase activity together with an increased interleukin-10 (IL-10) production, whereas they showed a decreased antigen-presenting ability and nitric oxide production. Keywords: alternatively activated macrophages; classically activated macrophages; immune tolerance; mouse; arginase Mononuclear phagocytes, an important part of innate immunity, have pivotal roles in pathogen and tissue debris clearance, antigen capture and presentation as well as in shaping the development of adaptive immune response. Macrophages are a highly heterogeneous cell population that adapt and respond to a large variety of microenvironmental signals. 1 Distinct macrophage subsets expressing different patterns of chemokines, surface markers and metabolic enzymes and showing diversity of functions can be induced in inflammatory and noninflammatory settings. 2-4 M1 (classically activated) macrophages, after induction by proinflammatory mediators, such as lipopolysaccharide (LPS), interleukin-1b (IL-1b) and interferon-g (IFN-g), produce significant amounts of proinflammatory cytokines (TNF-a, IFN-g, IL-6 and IL-12) and generate reactive oxygen species such as nitric oxide (NO) by activation of inducible nitric oxide synthase (Nos2). [2][3][4] In contrast, M2 (alternatively activated) macrophages, which are induced by exposure to IL-4, IL-13, IL-10, transforming growth factor-b (TGF-b) and glucocorticoids, produce less proinflammatory cytokines and instead, simultaneously also show more production of anti-inflammatory cytokines IL-10, TGF-b and IL-1 receptor antagonist as well as enzyme arginase. 2,5,6 Furthermore, M2 macrophages express high levels of CD206 and CD163. Overall, M2 macrophages are believed to participate in the blockade of inflammatory responses and promotion of tissue repair and type II immunity. 7,8 Importantly, recent studies have shown that M2 macrophages, which are different from M1 macrophages, have been implicated in controlling CD4 + T-cell hyporesponsiveness by inducing CD4 + CD25 + Treg cells or inhibiting IL-17-producing CD4 + T cells (Th17) in autoimmunity, transplant immunity or pathogenic infections. 9-11 These studies indicate that different macrophage subsets have distinguished roles in modulating immune response or tolerance.It is now known that CD4 + CD25 + regulatory T cells (Treg cells), which e...

Key Points rhTPO is a potentially effective and safe treatment option for ITP during pregnancy.

Amyotrophic lateral sclerosis, a devastating neurodegenerative disease, is characterized by the progressive loss of motor neurons and the accumulation of misfolded protein aggregates. The latter suggests impaired proteostasis may be a key factor in disease pathogenesis, though the underlying mechanisms leading to the accumulation of aggregates is unclear. Further, recent studies have indicated that motor neuron cell death may be mediated by astrocytes. Herein we demonstrate that ALS patient iPSC-derived astrocytes modulate the autophagy pathway in a non-cell autonomous manner. We demonstrate cells treated with patient derived astrocyte conditioned medium demonstrate decreased expression of LC3-II, a key adapter protein required for the selective degradation of p62 and ubiquitinated proteins targeted for degradation. We observed an increased accumulation of p62 in cells treated with patient conditioned medium, with a concomitant increase in the expression of SOD1, a protein associated with the development of ALS. Activation of autophagic mechanisms with Rapamycin reduces the accumulation of p62 puncta in cells treated with patient conditioned medium. These data suggest that patient astrocytes may modulate motor neuron cell death by impairing autophagic mechanisms, and the autophagy pathway may be a useful target in the development of novel therapeutics.

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