Current Immunology Reviews

ISSN: 1573-3955

Current Immunology Reviews
Volume 4, Number 2, May 2008

Contents


PROGRAMMED Cell Clearance: Molecular Mechanisms and Role in Autoimmune Disease, Chronic Inflammation, and Anti-Cancer Immune Responses Pp. 53-69
Erika Witasp, Valerian Kagan and Bengt Fadeel
[Abstract]


Leptin and Inflammation Pp. 70-79
Noriko Iikuni, Queenie Lai Kwan Lam, Liwei Lu, Giuseppe Matarese and Antonio La Cava
[Abstract]


Inhibitory MHC Class I Receptors on Myeloid Cells Pp. 80-87
Akira Nakamura and Toshiyuki Takai
[Abstract]


Immunoglobulin Free Light Chains in Immune Responses Pp. 88-100
Joris van der Veeken and Frank A. Redegeld
[Abstract]


Pleiotropic Roles of Runx Transcription Factors in the Differentiation and Function of T Lymphocytes Pp. 101-115
Kazuyoshi Kohu, Masato Kubo, Hitoshi Ichikawa, Shinichiro Ohno, Sonoko Habu, Takehito Sato and Masanobu Satake
[Abstract]




Abstracts

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PROGRAMMED Cell Clearance: Molecular Mechanisms and Role in Autoimmune Disease, Chronic Inflammation, and Anti-Cancer Immune Responses
Erika Witasp, Valerian Kagan and Bengt Fadeel

During normal development and tissue turnover, cells are programmed to undergo apoptosis and cell corpses are subsequently removed by professional phagocytes (macrophages) or other neighboring cells. The recognition and engulfment of apoptotic cell corpses, a complex and dynamic process which we have termed programmed cell clearance, is thought to prevent chronic inflammation through the disposal of dying cells prior to the leakage from these cells of noxious constituents into surrounding tissues. Moreover, rapid engulfment of apoptotic cells, orchestrated through the interaction of numerous recognition or “eat- me” signals, bridging molecules, and engulfment receptors, is believed to prevent inadvertent immune responses to self antigen present within or on the surface of dying cells. Finally, while engulfment of apoptotic cells is generally considered to be a silent process from an immunological perspective, recognition and uptake of apoptotic cell corpses by antigen-presenting dendritic cells may in some cases trigger an immunogenic response, suggesting that the process of programmed cell clearance could be harnessed for therapeutic purposes to improve cancer treatment. The present review will discuss the molecular mechanisms of programmed cell clearance, as well as the role of this fundamental process in inflammation, autoimmune disease, and anti cancer immune responses.


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Leptin and Inflammation
Noriko Iikuni, Queenie Lai Kwan Lam, Liwei Lu, Giuseppe Matarese and Antonio La Cava

The past few years of research on leptin have provided important information on the link between metabolism and immune homeostasis. Adipocytes influence not only the endocrine system but also the immune response through several cytokine-like mediators known as adipokines, which include leptin. It is widely accepted that leptin can directly link nutritional status and pro-inflammatory T helper 1 immune responses, and that a decrease of leptin plasma concentration during food deprivation can lead to an impaired immune function. Additionally, several studies have implicated leptin in the pathogenesis of chronic inflammation, and the elevated circulating leptin levels in obesity appear to contribute to the low-grade inflammatory background which makes obese individuals more susceptible to increased risk of developing cardiovascular diseases, type II diabetes, or degenerative disease including autoimmunity and cancer. Conversely, reduced levels of leptin such as those found in malnourished individuals have been linked to increased risk of infection and reduced cell-mediated immune responses. We discuss here the functional influences of leptin in the physiopathology of inflammation, and the effects of leptin in the modulation of such responses.


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Inhibitory MHC Class I Receptors on Myeloid Cells
Akira Nakamura and Toshiyuki Takai

Inhibitory MHC class I receptors are mainly expressed on NK cells. NK cells bear various kinds of inhibitory MHC class I receptors, Killer cell immunoglobulin (Ig)-like receptors, CD94/NKG2A hetrodimer, and murine Ly49 receptor family for monitoring the expression of MHC class I on surrounding cells. Leukocyte Ig-like receptors (LILRs), which bind MHC class I molecules, are expressed on other immune cells, such as B cells, macrophages, dendritic cells (DCs) and mast cells. A murine LILR relative, paired Ig-like receptor (PIR), which is expressed on B cells and myeloid cells but not on NK and T cells, also recognizes MHC class I molecules as its ligand. Recent studies have revealed that some of these inhibitory receptors associate with MHC class I on the same cell surface (in cis). Moreover, the cis-interaction has been verified to regulate effector functions of NK cells or myeloid cells. In this review, we summarize recent discoveries on the functions of inhibitory MHC class I receptors, and discuss their regulatory roles in immune responses.


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Immunoglobulin Free Light Chains in Immune Responses
Joris van der Veeken and Frank A. Redegeld

The functional activity of immunoglobulin free light chains in mast cell dependent hypersensitivity-like responses implicates a potential role for these molecules in other immune disorders. Mast cell-bound immunoglobulin free light chains recognize antigen and induce mast cell activation and mediator release. Through this mechanism, immunoglobulin free light chains can contribute to the pathogenesis of e.g. contact hypersensitivity and non-atopic asthma. These findings shed new light on the potential role of immunoglobulin free light chains in autoimmune disorders, such as multiple sclerosis and rheumatoid arthritis. Immunoglobulin free light chain levels are increased in these disorders and correlate with disease activity. Further establishing the contribution of immunoglobulin free light chain-mediated mast cell activation to the pathogenesis of chronic inflammatory diseases may lead to novel therapeutic strategies in their treatment.


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Pleiotropic Roles of Runx Transcription Factors in the Differentiation and Function of T Lymphocytes
Kazuyoshi Kohu, Masato Kubo, Hitoshi Ichikawa, Shinichiro Ohno, Sonoko Habu, Takehito Sato and Masanobu Satake

The proteins of the Runx gene family are among the most important transcription factors for regulating the differentiation and function of T lymphocytes. Runx1 and Runx3 are each involved in multiple and distinct steps throughout the process of T-cell differentiation. Targeted disruption or transgenic overexpression of the Runx genes causes pleiotropic and pathological phenotypes, including cell differentiation arrest, abnormal growth or survival, and immunological disorders. Runx proteins exert positive or negative effects on the transcription of a variety of possible target genes, depending on the context of the promoter, enhancer, and silencer. We now have a basic understandin of Runx function. To fully understand T-lymphocyte differentiation and function, the next challenge will be to investigate how Runx, as a member of a regulatory network, works in cooperation with TCR/cytokine receptor signaling and other transcriptionrelated factors.