Skip to main content.

Journal Menu

Sales and Services

Wiley-Blackwell

Search Catalog

Editor's Choice - June 2009

Li-Fan Lu and Adrian Liston
MicroRNA in the immune system, microRNA as an immune system
Immunology
Volume 127, Issue 3, Pages 291-298
doi: 10.1111/j.1365-2567.2009.03092.x

Through the modulation of transcription and translation, microRNA alter the basal state of cells and the outcome of stimulatory events. In addition to regulating key processes in the immune system, microRNA may also represent an archaic immune system themselves. Small interfering RNA of viral origin has been shown to function as an intracellular mediator in the suppression of viral infection in eukaryotes as diverse as plants, insects, nematodes and fungi, and there is growing evidence that endogenous mammalian microRNA can have similar impacts. In this article, Liston & Lu speculate that the anti-viral function of microRNA drove the expression of different subsets of microRNA in different cellular lineages, which may have, in turn, led to the myriad of roles microRNA play in lineage differentiation and stability.

Emily A. Stevens, Joshua D. Mezrich and Christopher A. Bradfield
The aryl hydrocarbon receptor: a perspective on potential roles in the immune system
Immunology
Volume 127, Issue 3, Pages 299-311
doi: 10.1111/j.1365-2567.2009.03054.x

The aryl hydrocarbon receptor (AHR) is a protein best known for its role in mediating toxicity. Over 30 years of research has uncovered additional roles for the AHR in xenobiotic metabolism and normal vascular development. Activation of the AHR has long been known to cause immunotoxicity, including thymic involution. Recent data suggesting a role for the AHR in regulatory T-cell (Treg) and T-helper 17 (Th17) cell development have only added to the excitement about this biology. In this review, Bradfield et al. illustrate what is currently known about AHR biology in the hope that data from fields as diverse as evolutionary biology and pharmacology will help elucidate the mechanism by which AHR modifies immune responses.

Editor's Choice - May 2009

Christina Falschlehner, Uta Schaefer and Henning Walczak
Following TRAIL's path in the immune system
Immunology
Volume 127, Issue 2, Pages 145-154
doi: 10.1111/j.1365-2567.2009.03058.x

The TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) belongs to the subfamily of ligands that is responsible for extrinsic induction of cell death. Depending on their status of stimulation, TRAIL can be expressed by various cells of the immune system. TRAIL has been implicated in immunosuppressive, immunoregulatory and immune-effector functions. With respect to pathological challenges, TRAIL and its receptors have been shown to play important roles in the immune response to viral infections and in immune surveillance of tumours and metastases. In this review Walczak et al. summarise the current knowledge on the role of TRAIL and its receptors in the immune system and, based on this, discuss future directions of research into the diverse functions of this fascinating receptor–ligand system.

Katarzyna Placek, Maryaline Coffre, Sylvie Maiella, Elisabetta Bianchi and Lars Rogge
Genetic and epigenetic networks controlling T helper 1 cell differentiation
Immunology
Volume 127, Issue 2, Pages 155-162
doi: 10.1111/j.1365-2567.2009.03059.x

Significant progress has been made during the past years in our understanding of the mechanisms that control the differentiation of naïve CD4+ T cells into effector T-cell subsets with distinct functional properties. In this review Rogge et al. highlight advances that have been made in unravelling the genetic and epigenetic networks controlling differentiation of naïve CD4+ T cells into interferon-Υ(IFN-Υ)-secreting T helper type 1 (Th1) cells.

Editor's Choice - April 2009

Saman Eghtesad, Penelope A. Morel and Paula R. Clemens
The companions: regulatory T cells and gene therapy
Immunology
Volume 127, Issue 1, Pages 1-7
doi: 10.1111/j.1365-2567.2009.03069.x

Undesired immunological responses to products of therapeutic gene replacement have been obstacles to successful gene therapy. Understanding such responses of the host immune system to achieve immunological tolerance to a transferred gene product is therefore crucial. In this article, Clemens et al. review relevant studies of immunological responses to gene replacement therapy, the role of immunological tolerance mediated by regulatory T cells in down-regulating the unwanted immune responses, and the interrelationship of the two topics.

Katie J. Anderson and Rachel L. Allen
Regulatory T cells overturned: the effectors fight back
Immunology
Volume 127, Issue 1, Pages 8-17
doi: 10.1111/j.1365-2567.2009.03097.x

Following recognition of microbial patterns, innate immune receptors provide a rapid innate response and trigger antigen-presenting cell maturation to instruct adaptive immune responses. Here Allen & Anderson discuss a family of innate immune receptors for self – the leucocyte immunoglobulin-like receptors (LILRs). These LILRs exert powerful inhibitory effects on antigen-presenting cell phenotype and subsequent T-cell responses, and may act to constrain the effects of Toll-like receptor signalling. The relevance of LILR-mediated immune regulation across a range of scenarios from autoimmunity to transplant medicine, infection and cancer are discussed.

Editor's Choice - March 2009

Kuldeep Cheent and Salim I. Khakoo
Natural killer cells: integrating diversity with function
Immunology
Volume 126, Issue 4, Pages 449-457
doi: 10.1111/j.1365-2567.2009.03045.x

The key role of natural killer cells in many aspects of the immune response is now being recognised. The last decade has seen an exponential increase in our understanding of the workings of these cells. Receptor diversity is crucial in allowing natural killer cells to respond effectively to a variety of different pathogens. This paper from Cheent & Khakoo reviews aspects of natural killer cell diversity that combine to generate populations of functional natural killer cells that exist within both the individual and throughout the population at large.

Lucy S. K. Walker
Regulatory T cells overturned: the effectors fight back
Immunology
Volume 126, Issue 4, Pages 466-474
doi: 10.1111/j.1365-2567.2009.03053.x

It is now accepted that Tregs can target numerous cell populations to elicit potent immunosuppression. Intriguingly, emerging data suggest that certain signals can confer resistance to Treg suppression. Moreover, such resistance may be relevant to the pathogenesis of autoimmune diseases. Here Lucy Walker reviews various pathways linked to resistance to Treg suppression. These include Toll-like receptor (TLR) signals, cytokines and the triggering of TNF-receptor family members.

Editor's Choice - February 2009

Rafael Casellas, Arito Yamane, Alexander L. Kovalchuk and Michael Potter
Restricting activation-induced cytidine deaminase tumorigenic activity in B lymphocytes Immunology
Volume 126, Issue 3, Pages 316-328
doi: 10.1111/j.1365-2567.2008.03050.x

DNA breaks play an essential role in germinal centre B cells as intermediates to immunoglobulin class switching, a recombination process initiated by activation-induced cytidine deaminase (AID). Immunoglobulin gene hypermutation is likewise catalysed by AID but is believed to occur via single-strand DNA breaks. When improperly repaired, AID-mediated lesions can promote chromosomal translocations (CTs) that juxtapose the immunoglobulin loci to heterologous genomic sites, including oncogenes. Here Casellas et al. review recent advances and discuss the usage of pristane-induced mouse plasmacytomas as a tool to investigate the origin of Igh–cMyc translocations and B-cell tumorigenesis.

Sara A. Miller and Amy S. Weinmann
Common themes emerge in the transcriptional control of T helper and developmental cell fate decisions regulated by the T-box, GATA and ROR families
Immunology Volume 126, Issue 3, Pages 306-315
doi: 10.1111/j.1365-2567.2008.03040.x

Cellular differentiation requires the precise action of lineage-determining transcription factors. In the immune system, CD4+ T helper cells differentiate into at least three distinct effector lineages, Th1, Th2 and Th17, with the fate of the cell at least in part determined by the transcription factors T-bet, GATA-3 and ROR?t, respectively. Mutations in members of these transcription factor families are associated with a number of human genetic diseases due to a failure in completing lineage-specification events when the factor is dysregulated. As is explored in this paper by Weinmann & Miller, understanding the molecular events that contribute to the ability of T-bet, GATA-3 and ROR?t to define T helper cell lineages can provide valuable information relevant to the establishment of other developmental systems.

Editor's Choice - January 2009

Robert Zeiser, Kristina Maas, Sawsan Youssef, Christoph Dürr, Lawrence Steinman and Robert S. Negrin
Regulation of different inflammatory diseases by impacting the mevalonate pathway
Immunology

Published Online: 17 Dec 2008
doi: 10.1111/j.1365-2567.2008.03011.x

While initially developed for their lipid-lowering properties, statins have been extensively investigated with respect to their impact on autoantigen and alloantigen driven immune responses. It is shown that statins modify immune responses on several levels, including effects on dendritic cells, endothelial cells, macrophages, B cells and T cells, and several lines of evidence suggest that statins act in a disease-specific manner and are not effective in each immune disorder. This review from Negrin et al. discusses possible modes of action of statins in modulating immunity towards autoantigens and alloantigens.

Linda Wooldridge, Anna Lissina, David K. Cole, Hugo A. van den Berg, David A. Price and Andrew K. Sewell
Tricks with tetramers: how to get the most from multimeric peptide–MHC
Immunology

Volume 126, Issue 2, Pages 147-164
doi: 10.1111/j.1365-2567.2008.02848.x

The development of fluorochrome-conjugated peptide–major histocompatibility complex (pMHC) multimers in conjunction with continuing advances in flow cytometry has transformed the study of antigen-specific T cells by enabling their visualisation, enumeration, phenotypic characterization and isolation from ex vivo samples. Here, Sewell et al. bring together and discuss some of the 'tricks' that can be used to get the most out of pMHC multimers.

Editor's Choice - December 2008

Review Series

Helminths, Immune Modulation and the Hygiene Hypothesis

Graham A. W. Rook Review series on helminths, immune modulation and the hygiene hypothesis: The broader implications of the hygiene hypothesis Immunology 126 (1) 3-11 doi: 10.1111/j.1365-2567.2008.03007.x

Anne Cooke Review series on helminths, immune modulation and the hygiene hypothesis: How might infection modulate the onset of type 1 diabetes? Immunology 126 (1) 12-17 doi: 10.1111/j.1365-2567.2008.03009.x

Joseph A. Jackson, Ida M. Friberg, Susan Little and Janette E. Bradley Review series on helminths, immune modulation and the hygiene hypothesis: Immunity against helminths and immunological phenomena in modern human populations: coevolutionary legacies? Immunology 126 (1) 18-27 doi: 10.1111/j.1365-2567.2008.03010.x

Lucas Carvalho, Jie Sun, Colleen Kane, Fraser Marshall, Connie Krawczyk and Edward J. Pearce Review series on helminths, immune modulation and the hygiene hypothesis: Mechanisms underlying helminth modulation of dendritic cell function Immunology 126 (1) 28-34 doi: 10.1111/j.1365-2567.2008.03008.x

We are extremely pleased to publish an important review series on the subject of helminths, immune modulation and the hygiene hypothesis, from an eminent authorship. With the reconsideration of the Th1/Th2 model as a sole basis for understanding the latter, especially given the noted rise in incidence of non-Th2 mediated autoimmunities, the series is a timely consideration of current understanding. Danny Altmann has been hugely impressed by the insightful contributions from Graham Rook, Anne Cooke, Jan Bradley et al. and Ed Pearce et al.on different facets of the subject. This series will be available in print in the January issue of Immunology.

Meredith Mathis Curtis and Sing Sing Way
IL-17 in host defense against bacterial, mycobacterial, and fungal pathogens
Immunology Date received: 01-Nov-2008; Date accepted: 07-Nov-2008
doi: 10.1111/j.1365-2567.2008.03017.x

Here Curtis & Way examine the protective effects of the newly identified lineage of Th17 cells against pathogens like Klebsiella pneumoniae, Citrobacter rodentium, and Candida albicans, thus indicating their capacity to confer protection against extracellular bacterial and fungal pathogens, and thereby filling a critical void in host immunity not covered by the classically described Th1 lineage that activates immunity to intracellular pathogens, or the Th2 lineage important in protection to mucosal parasitic pathogens. This protection extends beyond that against extracellular bacterial and fungal pathogens, as demonstrated in infections against intracellular bacteria like Listeria monocytogenes and Salmonella enterica, as well as Mycobacterium tuberculosis. These insights are supported within the review both by experimental data in mouse infection models and epidemiological studies in humans. This is currently an Accepted Article.

Jennifer D. Stone, Adam S. Chervin, and David M. Kranz
T Cell Receptor Binding Affinities and Kinetics: Impact on T Cell Activity and Specificity
Immunology
Date received: 01-Nov-2008; Date accepted: 07-Nov-2008
doi: 10.1111/j.1365-2567.2008.03015.x

The interaction between the T cell receptor (TCR) and its pepMHC ligand plays a critical role in determining the activity and specificity of the T cell. The binding properties associated with these interactions have now been studied in many systems, providing a framework for a mechanistic understanding of the initial events that govern T-cell function. Here Kranz et al. provide an overview of four areas that directly impact our understanding of T cell function, as viewed from the perspective of the TCR:pepMHC interaction: (i) Relationships between T-cell activity and TCR:pepMHC binding parameters; (ii) TCR affinity, avidity, and clustering; (iii) Influence of co-receptors on pepMHC binding by TCRs and T-cell activity; and (iv) Impact of TCR binding affinity on antigenic peptide specificity. This is currently an Accepted Article.

Editor's Choice - November 2008

Rafal Pacholczyk and Joanna Kern
The T-cell receptor repertoire of regulatory T cells
Immunology 125 (4) 450-458
doi: 10.1111/j.1365-2567.2008.02992.x

The CD4+ CD25+ regulatory population of T cells (Treg cells) is the key component of the peripheral tolerance mechanism that protects us from a variety of autoimmune diseases. Experimental evidence shows that Treg cells recognize a wide range of antigenic specificities with increased reactivity to self antigens, although the affinity of these interactions remains to be further defined. In this review, Pacholczyk & Kern discuss how different features of the Treg repertoire influence our understanding of Treg specificities and the role of self reactivity in the generation of this population.

Pratip K. Chattopadhyay, Carl-Magnus Hogerkorp and Mario Roederer
A chromatic explosion: the development and future of multiparameter flow cytometry
Immunology 125 (4) 441-449
doi: 10.1111/j.1365-2567.2008.02989.x

Multiparameter flow cytometry has matured tremendously since the 1990s, giving rise to a technology that allows us to study the immune system in unprecedented detail. In this article, Chattopadhyay, Hogerkorp & Roederer review the development of hardware, reagents, and data analysis tools for multiparameter flow cytometry and discuss future advances in the field. Finally, we highlight new applications that use this technology to reveal previously unappreciated aspects of cell biology and immunity.

Editor's Choice - October 2008

Ruth C. Lovering, Evelyn B. Camon, Judith A. Blake, and Alexander D. Diehl
Access to immunology through the Gene Ontology
Immunology 125 (2) 154-160
doi: 10.1111/j.1365-2567.2008.02940.x

Following the highly readable introduction to the Gene Ontology (GO) presented in the May issue of Immunology News, Lovering et al. publish a further review that takes a closer look at the detailed workings of the GO, including instances of where it has provided novel research insights. This provides a further incentive for BSI members and immunologists in general, to get on board! Please note that Dr Lovering will be attending the BSI congress to discuss her work during one of the plenary sessions. She will also be manning a post in the exhibition hall to discuss her work on a one-to-one basis – full details will be given in the congress programme.

Megan E. Himmel, Gijs Hardenberg, Ciriaco A. Piccirillo, Theodore S. Steiner, and Megan K. Levings
The role of T-regulatory cells and Toll-like receptors in the pathogenesis of human inflammatory bowel disease
Immunology 125 (2) 145-153
doi: 10.1111/j.1365-2567.2008.02939.x

Inflammatory bowel disease (IBD) is thought to be the product of a combination of genetic and environmental factors that result in the abnormal regulation of immune responses. Experimental models have demonstrated that normal CD4+ T-regulatory (Treg) cell responses and commensal bacteria are required for the maintenance of gut immune homeostasis. Recent evidence that CD4+ T cells express Toll-like receptors (TLRs) and respond directly to TLR ligands, suggests that signals from commensal bacteria may directly affect T-cell responses in the gut. In this review, Levings et al. focus on evidence that defects in Treg cells may underlie IBD in humans. In addition, they discuss evidence that direct signaling via TLRs to T cells can affect IBD and that T-cell-dependent responses to bacterial proteins are central to the aetiology of this disease.

Rebecca C. Furze and Sara M. Rankin
Neutrophil mobilization and clearance in the bone marrow
Immunology 125 (3) 281-288
doi: 10.1111/j.1365-2567.2008.02950.x

Appropriate during this Metchnikoff centenary, Furze & Rankin take a fresh look at the familiar cell, key to innate immunity – the neutrophil. The bone marrow is the site of neutrophil production and following infection or inflammatory insult, neutrophil release from the bone marrow reserve is substantially elevated; this process being mediated by the co-ordinated actions of cytokines and chemokines. This review discusses the factors and molecular mechanisms regulating the neutrophil mobilisation and considers the mechanisms and functional significance of neutrophil clearance via the bone marrow.

Editor's Choice - September 2008

Arthur A. Vandenbark and Halina Offner
Critical evaluation of regulatory T cells in autoimmunity: are the most potent regulatory specificities being ignored?
Immunology 125 (1) 1-13
doi: 10.1111/j.1365-2567.2008.02900.x

The identification of CD4+ CD25+ Foxp3+ regulatory T (Treg) cells as natural regulators of immunity in the periphery and tissues has stimulated tremendous interest in developing therapeutic strategies for autoimmune diseases. Here Vandenbark & Offner evaluate the site of origin, antigen specificity, homing markers and cytokine profiles of Treg in autoimmune colitis and type 1 diabetes, two examples in which Treg cells were effective as therapy. These studies are compared with studies of Treg cells in experimental autoimmune encephalomyelitis and multiple sclerosis, where successful therapy has not yet been achieved. Antigen-specific Treg cells appear to have more potent activity than polyclonal Treg cells and therefore hold more promise as therapeutic agents. However, Treg cells specific for the pathogenic T effector cells themselves have largely been overlooked and deserve consideration in future studies.

Wendy W. C. van Maren, Joannes F. M. Jacobs,I. Jolanda M. de Vries, Stefan Nierkens and Gosse J. Adema
Toll-like receptor signalling on Tregs: to suppress or not to suppress?
Immunology 124 (4) 445-452
doi: 10.1111/j.1365-2567.2008.02871.x

The association of TLRs with innate activatory mechanisms is well established. Notably, recent studies have revealed that TLR2 signalling affects Treg expansion and function. This review from Adema et al. focuses on the presence and influence of different TLRs on T lymphocytes, including Tregs, and their role in cancer.

Editor's Choice - April 2008

Jane Gilmour and Paul Lavender
Control of IL-4 expression in T helper 1 and 2 cells
Immunology 124 (4) 437-444
doi: 10.1111/j.1365-2567.2008.02845.x

The mechanism of differentiation of naïve T cells to a variety of effector lineages, particularly Th1 and Th2 cells, has been the subject of intense scrutiny over the past two decades. Regulation of IL-4 expression has been of particular interest for two main reasons: first because IL-4 acts as a growth factor for Th2 cells, and second because of its role in the induction of immunoglobulin class switching to igE, which plays a critical role in mediating allergic responses. Study of the pathways that promote this tissue-restricted expression of IL-4 may highlight potential areas for therapeutic intervention and the current state-of-play is summarised in this review by Lavender & Gilmore.

Christy Toms, Heidi Jessup, Claire Thompson, Dilair Baban, Kay Davies and Fiona Powrie
Gpr83 expression is not required for the maintenance of intestinal immune homeostasis and regulation of T-cell-dependent colitis
Immunology (Early View Articles)
doi: 10.1111/j.1365-2567.2008.02857.x

Tregs are integral to the maintenance of intestinal homeostasis, where an intricate balance between tolerance and immunity must be maintained. Recently, studies have focused on the identification of molecules involved in the function and/or development of Tregs. One such molecule, Gpr83, has been identified through gene expression analysis as being overexpressed within thymic and peripheral naturally arising Treg populations (nTregs). This study from Powrie et al. aims to further define the characteristics of Gpr83 expression and to investigate the role of Gpr83 in Treg development and function through the generation and analysis of Gpr83-deficient mice.

Editor's Choice - November 2007

Daniel DiMeo, Jun Tian, Juan Zhang, Seiko Narushima, Daniel J. Berg
Increased interleukin-10 production and Th2 skewing in the absence of 5-lipoxygenase
Immunology (OnlineEarly Articles)
doi:10.1111/j.1365-2567.2007.02694.x

Eicosanoids (prostaglandins and leukotrienes) are important mediators of inflammatory responses. These lipid mediators may also regulate the production of peptide mediators of the immune system. In this study, Berg et al. investigated the effect of the absence of 5-lipoxygenase (5-LO)-derived leukotrienes on interleukin (IL)-10 production. IL-10 is a key regulator of immune and inflammatory responses, and previous studies have suggested that prostaglandins effect their immunosuppressive functions in part by stimulation of IL-10 production. Their findings indicate that, in addition to the central role leukotrienes play in the acute inflammatory response, endogenous leukotrienes are also important regulators of inflammatory cytokine production, via regulation of IL-10 production and in vivo differentiation of T cells.

A. G. Edwards, A. R. Weale, A. J. Denny, K. J. Edwards, C. R. Helps, P. A. Lear, M. Bailey
Antigen receptor V-segment usage in mucosal T cells
Immunology (OnlineEarly Articles)
doi:10.1111/j.1365-2567.2007.02685.x

Here Edwards et al. investigate aspects of the accepted model of lymphocyte intestinal homing, whereby naïve T cells are suggested to recirculate via organized lymphoid tissues, whilst induced effector/memory cells home to the intestinal mucosa – in a rat model.

Jacqueline Fischer-Lougheed, Clare Gregory, Zena White, Irina Shulkin, Mirja Gunthart, Mary Kearns-Jonker
Identification of an anti-idiotypic antibody that defines a B-cell subset(s) producing xenoantibodies in primates
Immunology (OnlineEarly Articles)
doi:10.1111/j.1365-2567.2007.02704.x

Synthetic anti-idiotypic antibodies represent a potentially valuable tool for the isolation and characterization of B cells that produce xenoantibodies. An anti-idiotypic antibody that binds to a subset of B cells producing antibodies encoded by the variable-region heavy chain 3 (VH3) germline genes DP35 [immunoglobulin variable-region heavy chain 3-11 (IGHV3-11)], DP-53 and DP-54 plus a small number of VH4 gene-encoded antibodies in humans has recently been identified. These germline progenitors also encode xenoantibodies in humans. Kearns-Jonker et al. tested whether the small, clearly defined group of B cells identified with this anti-idiotypic antibody produce xenoantibodies in non-human primates mounting active immune responses to porcine xenografts.

Editor's Choice - October 2007

Guangwei Liu, Yong Zhao
Toll-like receptors and immune regulation: their direct and indirect modulation on regulatory CD4+ CD25+ T cells
Immunology 122 (2), 149–156
doi:10.1111/j.1365-2567.2007.02651.x

The continued interdependence of the innate and adaptive immune responses is highlighted in this review by Zhao & Liu. There is an increasing body of evidence suggesting an immunoregulatory role for CD4+ CD25+ regulatory T cells across a number of disease domains. Toll-like receptor (TLR)-mediated recognition of specific structures of invading pathogens initiates innate as well as adaptive immune responses via antigen-presenting cells (APCs). New evidence suggests that TLR signalling may directly or indirectly regulate the immunosuppressive function of CD4+ CD25+ Treg cells in immune responses. This immunomodulation pathway may therefore have potential applications in the treatment of graft rejection, autoimmune diseases, infectious diseases and cancers.

Linda Mark, David G. Proctor, David J. Blackbourn, Anna M. Blom, O. Brad Spiller
Separation of decay-accelerating and cofactor functional activities of Kaposi's sarcoma-associated herpesvirus complement control protein using monoclonal antibodies
Immunology (OnlineEarly Articles)
doi:10.1111/j.1365-2567.2007.02692.x

Manipulation of the complement system by infective pathogens to promote survival is an acknowledged survival strategy. Kaposi's sarcoma-associated herpesvirus (KSHV) is the most recently identified human herpesvirus and the likely aetiological agent of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. KSHV complement control protein (KCP) is expressed on infected cells and virions, and could inhibit complement. Spiller et al. examined the ability of monoclonal anti-KCP antibodies to blockade KCP functions, relative to their recognized epitopes. Their results show that, while KCP is a multifunctional protein, these activities do not completely overlap and can be isolated through incubation with monoclonal antibodies.

Jasper Manning, Marie Indrova, Barbora Lubyova, Hana Pribylova, Jana Bieblova, Jiri Hejnar, Jana Simova, Tana Jandlova, Jan Bubenik, Milan Reinis
Induction of MHC class I molecule cell surface expression and epigenetic activation of antigen-processing machinery components in a murine model for human papilloma virus 16-associated tumours
Immunology (OnlineEarly Articles)
doi:10.1111/j.1365-2567.2007.02689.x

Reinis et al. investigated the up-regulation of major histocompatibility complex (MHC) class I surface expression on tumour cells by epigenetic mechanisms using a murine tumour cell line expressing human E6 and E7 human papilloma virus 16 (HPV16) oncogenes and deficient in MHC class I expression. Treatment of the cells with a histone deacetylase inhibitor, either alone or in combination with a DNA demethylating agent, induced surface re-expression of MHC class I molecules. Consequently, the treated cells became susceptible to lysis by specific cytotoxic T lymphocytes. The results demonstrate that expression of the genes involved in APM are modulated by epigenetic mechanisms and suggest that agents modifying DNA methylation and/or histone acetylation have the potential to change the effectiveness of antitumour immune responses and therapeutically may have an impact on immunological output.

Editor's Choice - September 2007

M. Gilchrist, A. D. Befus
Interferon-γ regulates chemokine expression and release in the human mast cell line HMC1: role of nitric oxide
Immunology (OnlineEarly Articles).
doi:10.1111/j.1365-2567.2007.02688.x

The role of interferon-γ (IFN-γ) in modulating the activity of mast cells (MCs) in the context of a human cell line is explored in this article by Gilchrist & Befus. As important immune effector cells, MCs have a role in both homeostasis and disease and, in the rodent, IFN-γ has been shown to modulate MC responsiveness via production of nitric oxide (NO). However, hitherto, the effects in human MC populations were unknown.

Konrad A. Bode, Kate Schroder, David A. Hume, Timothy Ravasi, Klaus Heeg, Matthew J. Sweet, Alexander H. Dalpke
Histone deacetylase inhibitors decrease Toll-like receptor-mediated activation of proinflammatory gene expression by impairing transcription factor recruitment
Immunology (OnlineEarly Articles).
doi:10.1111/j.1365-2567.2007.02678.x

Modulation of immune activity at the level of chromatin structure is explored in this article by Dalpke et al.. Activation of histone acetyltransferases or inhibition of histone deacetylases (HDACs) is generally believed to allow chromatin to assume a more open state, permitting transcriptional activity. The authors here report the intriguing observation that treatment of murine dendritic cells with the HDAC inhibitors trichostatin A (TSA) or suberoylanilide hydroxamic acid (SAHA) in non-apoptotic concentrations strongly inhibited induction of both interleukin-12 protein p40 (IL-12p40) mRNA and protein upon stimulation of Toll-like receptors (TLRs).

Nam-Hoon Kim, Mun-Yong Lee, Seon-Joo Park, Jeong-Sun Choi, Mi-Kyung Oh, In-Sook Kim
Auranofin blocks interleukin-6 signalling by inhibiting phosphorylation of JAK1 and STAT3
Immunology (OnlineEarly Articles).
doi:10.1111/j.1365-2567.2007.02679.x

Auranofin (AF) is a sulphur-containing gold compound widely used for the therapeutic treatment of rheumatoid arthritis because of its anti-inflammatory and immunosuppressive activities. Despite this, little is known about its mechanism of action. In this report Kim et al. help to further elucidate the molecular mechanism underlying the anti-inflammatory effect of AF, by studying the effects of AF on cellular responses to interleukin-6 (IL-6).