Search

Sirtuins are evolutionarily conserved class III histone deacetylases that have been the focus of intense scrutiny and interest since the discovery of Sir2 as a yeast longevity factor. Early reports demonstrated an important role of Sirt1 in aging and metabolism, but its critical regulatory role in the immune system has only been unveiled in recent years. In this review we discuss the latest advances in understanding the regulatory role of Sirt1 in immune responses as well as how Sirt1 translates metabolic cues to immune signals, which would bring new insights into both pathogenesis and potential therapeutic strategies of a variety of immune-related diseases, such as cancer, microbial infection, autoimmune diseases and transplantation. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase which has a central role in the regulation of cell growth and metabolism. In the study of the mTOR signaling pathway, tuberous sclerosis complex (TSC) 1/2 complex is identified as a critical regulator of mTOR activity. TSC1/2 plays important roles for immune cell homeostasis and differentiation by negative control of mTOR signaling pathway. TSC1/2-mTOR pathway is proving to be a central point in regulating immune function of diverse immune cells. In this review, we discuss the function of TSC1/2-mTOR to direct the innate and adaptive immune cell development and function. Furthermore, we focus on the role of TSC1/2-mTOR signaling pathway in immune cell mediated diseases, especially autoimmunity. J. Cell. Physiol. 229: 17-26, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The critical roles of kinase AKT in tumour cell proliferation, apoptosis and protein synthesis have been widely recognized. But AKT also plays an important role in immune modulation. Recent studies have confirmed that kinase AKT can regulate the development and functions of innate immune cells (neutrophil, macrophage and dendritic cell). Studies have shown that different isoforms of kinase AKT have different effects in regulating immunity-related diseases, mainly through the mammalian target of rapamycin-dependent or -independent pathways. The purpose of this review is to illustrate the immune modulating effects of kinase AKT on innate immune cell development, survival and function. [ABSTRACT FROM AUTHOR]

Macrophages are central mediators of the immune, contributing both to the initiation and the resolution of inflammation. The concept of macrophage activation and program has stimulated interest in its definition, and functional significance in homeostasis and diseases. It has been known that macrophages could be differently activated and programmed into different functional subtypes in response to different types of antigen stumuli or different kinds of cytokines present in the microenvironment and could thus profoundly influence immune responses, but little is known about the state and exact regulatory mechanism of macrophage activation and program from cell or molecular signaling level in immunity. In this review, we summarize the recent finding regarding the regulatory mechanism of macrophage activation and program toward M1 and M2, especially on M2 macrophages. J. Cell. Physiol. 228: 502-512, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The therapeutic effects of glucocorticoids on colitis and colitis-associated cancer are unclear. In this study, we investigated the therapeutic roles of glucocorticoids in acute experimental ulcerative colitis and colitis-associated cancer in mice and their immunoregulatory mechanisms. Murine acute ulcerative colitis was induced by dextran sulfate sodium (DSS) and treated with dexamethasone (Dex) at different doses. Dex significantly exacerbated the onset and severity of DSS-induced colitis and potentiated mucosal inflammatory macrophage and neutrophil infiltration, as well as cytokine production. Furthermore, under inflammatory conditions, the expression of the glucocorticoid receptor (GR) did not change significantly, while mammalian target of rapamycin (mTOR) signaling was higher in colonic epithelial cells than in colonic immune cells. The deletion of mTOR in intestinal epithelial cells, but not that in myeloid immune cells, in mice significantly ameliorated the severe course of colitis caused by Dex, including weight loss, clinical score, colon length, pathological damage, inflammatory cell infiltration and pro-inflammatory cytokine production. These data suggest that mTOR signaling in intestinal epithelial cells, mainly mTORC1, plays a critical role in the Dex-induced exacerbation of acute colitis and colitis-associated cancer. Thus, these pieces of evidence indicate that glucocorticoid-induced mTOR signaling in epithelial cells is required in the early stages of acute ulcerative colitis by modulating the dynamics of innate immune cell recruitment and activation. [ABSTRACT FROM AUTHOR]

In response to different microenvironmental stimuli, macrophages are polarized into two populations, M1 macrophages which are classically activated by interferon (IFN)-γ with lipopolysaccharides (LPSs) and M2 macrophages which are alternatively activated by interleukin-4 (IL-4), to perform specific roles in innate immune responses. Accordingly, macrophages occupy distinct metabolic profiles, regulated by orchestrated factors and signaling pathways, including the PI3K-AKT, HIF, c-Myc, AMPK, and PPARs pathways. These factors and pathways play pivotal roles not only in metabolic regulation but also in macrophage polarization. After activation, classically activated M1 macrophages and alternatively activated M2 macrophages display distinct patterns in glucose, lipid, amino acid and iron metabolism. Here, we summarized recently discovered metabolism-related inflammatory signaling factors, along with reprogrammed metabolism, after the activation of macrophages under conditions related to immunity and cancer. Additionally, macrophage regulatory roles in infectious diseases, cancer progression and anti-cancer immunotherapy are discussed in terms of metabolic profiles, providing insight into the prevention and treatment of immune-associated diseases. [ABSTRACT FROM AUTHOR]