Hot off the presses! Feb 01

The Feb 01 issue of the is now up on Pubget (About ): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• From the editors
  - Nature Reviews Immunology 10(2):79 (2010)
  Several articles this month look at the inputs to and outputs from innate immune cells that determine their instructive role in shaping adaptive immune responses.The recognition of cytoplasmic DNA by innate immune cells is important for defence against viruses and many types of bacteria.
• Comment: Why does immunity to parasites take so long to develop?
  - Nature Reviews Immunology 10(2):80 (2010)
  To ensure successful transmission and establish chronic infection, parasites must evade the host's immune system and delay the development of immunity. Maria Yazdanbakhsh and David Sacks discuss how this might be achieved.
• Inflammation: TLRs find a partner in crime
  - Nature Reviews Immunology 10(2):82 (2010)
  A recent study published in Nature Immunology describes a new mechanism of sterile inflammation that is common to atherosclerosis and Alzheimer's disease. It shows that the recognition of altered self components that aggregate in plaques in these two diseases by the scavenger receptor CD36 triggers the assembly of Toll-like receptor 4 (TLR4) and TLR6 heterodimers, leading to the induction of pro-inflammatory responses that underlie the pathology of these diseases.
• T cell activation: A silent toll for T cells
  - Nature Reviews Immunology 10(2):83 (2010)
  Toll-like receptors (TLRs) have well-described roles in activating innate immune cell populations, but although T cells have also been shown to express TLRs, their function in these adaptive immune cells remains unclear. Now, a study by Raz and colleagues shows that TLR4 signalling in T cells can negatively regulate activation signals delivered by the T cell receptor (TCR).
• In brief: Neuroimmunology, Innate immunity, Tumour immunology
  - Nature Reviews Immunology 10(2):83 (2010)
  Dual roles for perivascular macrophages in immune-to-brain signaling Serrats, J.et al. Neuron, 94–106 (2010)Cytokines, produced during infection and/or inflammation, are known to activate the hypothalamic–pituitary–adrenal (HPA) axis through the induction of prostanoid production by vascular cells.
• Immune evasion: Bordetella escapes by inducing IL-10
  - Nature Reviews Immunology 10(2):84 (2010)
  Similarly to many bacterial pathogens, Bordetella bronchiseptica, which has been used for the study of Bordetella pertussis pathogenesis, manipulates the host immune response to promote its own survival by enhancing the production of the anti-inflammatory cytokine interleukin-10 (IL-10). A study by Nagamatsu et al.B. bronchiseptica
• Antigen presentation: Monotonous MHC sing in troubled times
  - Nature Reviews Immunology 10(2):84 (2010)
  Mouse Qa-1b and its human homologue, HLA-E, are highly conserved MHC class I-like molecules that protect host cells from cytotoxic lymphocytes by presenting a single self peptide, Qa-1 determinant modifier (Qdm) from the signal sequence of classical MHC class I molecules, to inhibitory natural killer (NK)-type receptors. Now, a study by Oliveira et al.b-bound Qdm is replaced with a diverse range of self peptides and this leads to elimination of these cells by CD8+ cytotoxic T lymphocytes (CTLs).
• In brief: NK cells, Tumour immunology, Autoimmunity
  - Nature Reviews Immunology 10(2):84 (2010)
  The activating receptor NKp46 is essential for the development of type 1 diabetes Gur, C.et al. Nature Immunol.20 Dec 2009 (doi: 10.1038/ni.1834)
• Innate immunity: 'Natural helper' cells identified
  - Nature Reviews Immunology 10(2):85 (2010)
  A recent paper published in Nature describes a new population of innate lymphocytes that are found in a previously unrecognized lymphoid structure associated with adipose tissue. The authors propose that these T helper 2 (TH2)-type innate lymphocytes be termed 'natural helper' cells.
• Lymphomagenesis: Far, far away
  - Nature Reviews Immunology 10(2):86 (2010)
  Translocations involving the immunoglobulin heavy chain (Igh) locus and Myc are oncogenic, but the elements that are involved in activating the transcription of these fusion genes have not been resolved. Gostissa et al.Igh 3′ regulatory region (Igh3′RR) can function over long distances to activate the transcription of translocated Myc.
• T cell responses: mTOR mixes up a recipe for success
  - Nature Reviews Immunology 10(2):86 (2010)
  The stimulation of naive CD8+ T cells to generate a successful effector response requires three main ingredients: antigen and co-stimulation for T cell activation and cytokine stimulation to determine the type of response. But like most recipes, the result depends on careful mixing.
• Tolerance: How AIRE wakes up sleepy genes
  - Nature Reviews Immunology 10(2):87 (2010)
  Immune tolerance to peripheral tissue antigens begins in the thymus, where medullary thymic epithelial cells (mTECs) give differentiating thymocytes a 'sneak preview' of the self antigens they will encounter in the periphery — a process that partially depends on the transcriptional regulator protein autoimmune regulator (AIRE). By looking at the binding partners of AIRE, this study puts forward a new model for how AIRE regulates the transcriptional 'waking' of peripheral tissue antigen genes in mTECs.
• Tumour immunology: Liver X factor helps tumours escape
  - Nature Reviews Immunology 10(2):88 (2010)
  The liver X receptors (LXRα and LXRβ) are transcription factors that are important for lipid and cholesterol homeostasis. Recent work has suggested that LXR signalling can also regulate innate and adaptive immune responses.
• Flu vaccine surplus
  - Nature Reviews Immunology 10(2):88 (2010)
  Recent vaccine trial data provided hope in the fight against swine flu by suggesting that a single dose of vaccine, and not two doses as initially thought, is sufficient to confer protection against the pandemic H1N1 strain of influenza virus (Nature Rev. Immunol.
• The IL-1 family: regulators of immunity
  - Nature Reviews Immunology 10(2):89 (2010)
  Over recent years it has become increasingly clear that innate immune responses can shape the adaptive immune response. Among the most potent molecules of the innate immune system are the interleukin-1 (IL-1) family members. These evolutionarily ancient cytokines are made by and act on innate immune cells to influence their survival and function. In addition, they act directly on lymphocytes to reinforce certain adaptive immune responses. This Review provides an overview of both the long-established and more recently characterized members of the IL-1 family. In addition to their effects on immune cells, their involvement in human disease and disease models is discussed.
• Disease-associated functions of IL-33: the new kid in the IL-1 family
  - Nature Reviews Immunology 10(2):103 (2010)
  Interleukin-33 (IL-33), a newly described member of the IL-1 family, is expressed by many cell types following pro-inflammatory stimulation and is thought to be released on cell lysis. The IL-33 receptor, consisting of ST2 and IL-1 receptor accessory protein, is also widely expressed, particularly by T helper 2 (TH2) cells and mast cells. IL-33 is host-protective against helminth infection and reduces atherosclerosis by promoting TH2-type immune responses. However, IL-33 can also promote the pathogenesis of asthma by expanding TH2 cells and mediate joint inflammation, atopic dermatitis and anaphylaxis by mast cell activation. Thus IL-33 could be a new target for therapeutic intervention across a range of diseases.
• Physiological and pathological roles for microRNAs in the immune system
  - Nature Reviews Immunology 10(2):111 (2010)
  Mammalian microRNAs (miRNAs) have recently been identified as important regulators of gene expression, and they function by repressing specific target genes at the post-transcriptional level. Now, studies of miRNAs are resolving some unsolved issues in immunology. Recent studies have shown that miRNAs have unique expression profiles in cells of the innate and adaptive immune systems and have pivotal roles in the regulation of both cell development and function. Furthermore, when miRNAs are aberrantly expressed they can contribute to pathological conditions involving the immune system, such as cancer and autoimmunity; they have also been shown to be useful as diagnostic and prognostic indicators of disease type and severity. This Review discusses recent advances in our understanding of both the intended functions of miRNAs in managing immune cell biology and their pathological roles when their expression is dysregulated.
• Intracellular DNA recognition
  - Nature Reviews Immunology 10(2):123 (2010)
  The recognition of nucleic acids is one strategy by which cells can detect infectious agents. As life is ultimately determined by the existence of nucleic acids, this defence strategy has evolved in many different organisms and operates effectively in many different cell types. Here, we review the recent progress in our understanding of the molecular mechanisms by which DNA activates cells to induce inflammation and antimicrobial immunity. DNA can be detected in different cellular compartments and can induce a range of cellular responses, such as an antiviral response and pyroptotic cell death together with the maturation and release of active interleukin-1β.
• Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function
  - Nature Reviews Immunology 10(2):131 (2010)
  A single layer of epithelial cells lines the small and large intestines and functions as a barrier between commensal bacteria and the rest of the body. Ligation of Toll-like receptors (TLRs) on intestinal epithelial cells by bacterial products promotes epithelial cell proliferation, secretion of IgA into the gut lumen and expression of antimicrobial peptides. As described in this Review, this establishes a microorganism-induced programme of epithelial cell homeostasis and repair in the intestine. Dysregulation of this process can result in chronic inflammatory and over-exuberant repair responses, and it is associated with the development of colon cancer. Thus, dysregulated TLR signalling by intestinal epithelial cells may explain how colonic bacteria and inflammation promote colorectal cancer.
• Surrogate end points in the design of immunotherapy trials: emerging lessons from type 1 diabetes
  - Nature Reviews Immunology 10(2):145 (2010)
  Approximately 5% of people in developed countries suffer from 1 of ~80 classified autoimmune diseases. The sheer scale of the clinical problem captures the interests of health policy makers, academics, funding bodies and pharmaceutical companies in equal measure. In recent decades, immunologists have gained a good understanding of disease pathogenesis, which has led to the development of various potential therapies. The next challenge is to establish which therapies have superior efficacy, sustainability and safety. Therapeutic trials that depend on clinical end points are long lasting and expensive. In this Opinion article we offer a perspective on the future of clinical trial design in which the process is significantly shortened by making greater use of laboratory measures to determine therapeutic outcome.