Hot off the presses! Jun 01 Nat Rev Immunol

The Jun 01 issue of the Nat Rev Immunol is now up on Pubget (About Nat Rev Immunol): 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
  - Nat Rev Immunol 10(6):377 (2010)
  When Élie Metchnikoff shared the Nobel Prize in 1908 with Paul Ehrlich, it marked the recognition of synergism in the immune system between cellular (phagocytic) and humoral (antibody) components. However, not until 1989, when Charles Janeway Jr postulated the hypothesis of pattern recognition receptors for pathogens, did phagocytes and innate immunity once again come to the fore.
• HIV: Calculating control
  - Nat Rev Immunol 10(6):379 (2010)
  A new study based on computer modelling brings us a step closer to understanding why certain individuals can control HIV infection for long periods of time without therapy. The authors predict that expression of the HLA-B57 allele by these individuals generates a naive CD8+ T cell repertoire that has a larger fraction of cells that recognize the virus and that these cells are more cross-reactive to mutants of targeted viral epitopes, features that may contribute to improved control of HIV.
• Innate immunity: Experience helps
  - Nat Rev Immunol 10(6):380 (2010)
  The mechanisms involved in the recognition of pathogens by innate immune cells and the subsequent induction of adaptive immunity are well known. But can cells of the adaptive immune system regulate innate inflammatory responses?
• T cell responses: PU.1 in time saves nine
  - Nat Rev Immunol 10(6):380 (2010)
  The differentiation of T helper (TH) cell subsets is controlled by unique sets of transcription factors; these regulate the expression of cytokines and other genes that are important for the effector functions of each subset. Recent reports have described an interleukin-9 (IL-9)-producing population of T cells, which is induced in vitro following culture with IL-4 and transforming growth factor-β (TGFβ).
• Therapeutic cancer vaccine approved
  - Nat Rev Immunol 10(6):380 (2010)
  The world's first therapeutic cancer vaccine has been approved by the US Food and Drug Administration (FDA), heralding a major breakthrough in the struggle to harness the immune system to fight tumours.The new vaccine, Provenge (sipuleucel-T), will be used to treat men with advanced prostate cancer and is tailored to the individual: each patient's immune cells are isolated and primed against tumour-specific antigens in vitro before being infused back into the patient (New York Times, 30 Apr 2010).
• In brief: Innate immunity, Cytokines, Antibody responses
  - Nat Rev Immunol 10(6):381 (2010)
  NLRC5 negatively regulates the NF-κB and type I interferon signaling pathways Cui, J.et al. Cell 141, 483–496 (2010)NLRC5 (NLR family, CARD containing 5) is a member of the NOD-like receptor family of intracellular pathogen recognition receptors, but its physiological function is not known.
• Cytokines: Cytokines reach out
  - Nat Rev Immunol 10(6):382 (2010)
  It is generally thought that interferon-γ (IFNγ) and interleukin-4 (IL-4) (the canonical T helper 1 (TH1)-type and TH2-type cytokines, respectively) function locally and only activate those cells that are in close proximity to the cytokine source. Perona-Wright et al.
• Innate immunity: The stress connection
  - Nat Rev Immunol 10(6):382 (2010)
  Smoking and prolonged stress have been linked to increased susceptibility to bacterial infection. New research in Cell Host & Microbe now shows that this may be caused by a decrease in antimicrobial peptide (AMP) activity as a result of increased stimulation of a neuroendocrine signalling pathway.
• V(D)J recombination: RAG recombination centres
  - Nat Rev Immunol 10(6):383 (2010)
  The recombination of variable (V), diversity (D) and joining (J) gene segments that form immunoglobulins and T cell receptors is essential for the generation of a highly diverse repertoire of antigen receptors. V(D)J recombination is initiated by binding of recombination-activating gene 1 (RAG1) and RAG2 to recombination signal sequences (RSSs) that flank these gene segments.
• Natural killer T cells: Limiting B cell autoimmunity
  - Nat Rev Immunol 10(6):384 (2010)
  The production and deposition of autoantibodies by B cells is a cardinal feature of systemic lupus erythematosus (SLE). Defective apoptotic cell clearance, as well as decreased numbers of invariant natural killer T (iNKT) cells, has been described in patients with SLE; however, whether these two observations are linked — and if so, how — is not known.
• T cells: TLRs deliver a direct hit to TH17 cells
  - Nat Rev Immunol 10(6):384 (2010)
  Toll-like receptors (TLRs) generally promote adaptive immune responses indirectly by activating innate immune cells. Now, new research shows an unexpected direct role for TLR2 signalling in T cells themselves, promoting the differentiation and proliferation of T helper 17 (TH17) cells.
• Innate immunity: A chain reaction
  - Nat Rev Immunol 10(6):385 (2010)
  New research published in Cell adds to the evidence indicating a crucial role for protein ubiquitylation in regulating immune responses. But in this example, free polyubiquitin chains in the cytoplasm — rather than the direct ubiquitylation of immune factors — are important for activating innate antiviral immunity.
• In brief: Innate immunity, Immune regulation, T cell development
  - Nat Rev Immunol 10(6):385 (2010)
  Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology Buonocore, S.et al. Nature 464, 1371–1375 (2010)The production of interleukin-17 (IL-17) and interferon-γ (IFNγ) during colitis is often attributed to CD4+ T cells.
• The SYK tyrosine kinase: a crucial player in diverse biological functions
  Mócsai A Ruland J Tybulewicz VL - Nat Rev Immunol 10(6):387 (2010)
  Spleen tyrosine kinase (SYK) is known to have a crucial role in adaptive immune receptor signalling. However, recent reports indicate that SYK also mediates other, unexpectedly diverse biological functions, including cellular adhesion, innate immune recognition, osteoclast maturation, platelet activation and vascular development. SYK is activated by C-type lectins and integrins, and activates new targets, including the CARD9–BCL-10–MALT1 pathway and the NLRP3 inflammasome. Studies using Drosophila melanogaster suggest that there is an evolutionarily ancient origin of SYK-mediated signalling. Moreover, SYK has a crucial role in autoimmune diseases and haematological malignancies. This Review summarizes our current understanding of the diverse functions of SYK and how this is being translated for therapeutic purposes.
• Cross-priming in health and disease
  Kurts C Robinson BW Knolle PA - Nat Rev Immunol 10(6):403 (2010)
  Cross-priming is an important mechanism to activate cytotoxic T lymphocytes (CTLs) for immune defence against viruses and tumours. Although it was discovered more than 25 years ago, we have only recently gained insight into the underlying cellular and molecular mechanisms, and we are just beginning to understand its physiological importance in health and disease. Here we summarize current concepts on the cross-talk between the immune cells involved in CTL cross-priming and on its role in antimicrobial and antitumour defence, as well as in immune-mediated diseases.
• Securing the immune tightrope: mononuclear phagocytes in the intestinal lamina propria
  Varol C Zigmond E Jung S - Nat Rev Immunol 10(6):415 (2010)
  The intestinal landscape comprises the host's own tissue and immune cells, as well as a diverse intestinal microbiota. Intricate regulatory mechanisms have evolved to maintain peaceful coexistence at this site, the breakdown of which can result in devastating inflammatory bowel diseases (IBDs). Mononuclear phagocytes promote both innate and adaptive immune responses in the gut and, as such, are essential for the maintenance of intestinal homeostasis. Here, we review the origins and functions of the mononuclear phagocytes found in the intestinal lamina propria, highlighting the problems that have arisen from their classification. Understanding these cells in their physiological context will be important for developing new therapies for IBDs.
• Phagocyte partnership during the onset and resolution of inflammation
  Soehnlein O Lindbom L - Nat Rev Immunol 10(6):427 (2010)
  Neutrophils, monocytes and macrophages are closely related phagocytic cells that cooperate during the onset, progression and resolution of inflammation. This Review highlights the mechanisms involved in the intimate partnership of phagocytes during each progressive phase of the inflammatory response. We describe how tissue-resident macrophages recognize tissue damage to promote the recruitment of neutrophils and the mechanisms by which infiltrating neutrophils can then promote monocyte recruitment. Furthermore, we discuss the phagocyte-derived signals that abrogate neutrophil recruitment and how the uptake of apoptotic neutrophils by macrophages leads to termination of the inflammatory response. Finally, we highlight the potential therapeutic relevance of these interactions.
• Mast cell-orchestrated immunity to pathogens
  Abraham SN St John AL - Nat Rev Immunol 10(6):440 (2010)
  Although mast cells were discovered more than a century ago, their functions beyond their role in allergic responses remained elusive until recently. However, there is a growing appreciation that an important physiological function of these cells is the recognition of pathogens and modulation of appropriate immune responses. Because of their ability to instantly release several pro-inflammatory mediators from intracellular stores and their location at the host–environment interface, mast cells have been shown to be crucial for optimal immune responses during infection. Mast cells seem to exert these effects by altering the inflammatory environment after detection of a pathogen and by mobilizing various immune cells to the site of infection and to draining lymph nodes. Interestingly, the character and timing of these responses can vary depending on the type of pathogen stimulus, location of pathogen recognition and sensitization state of the responding mast cells. Rec! ent studies using mast cell activators as effective vaccine adjuvants show the potential of harnessing these cells to confer protective immunity against microbial pathogens.
• Unravelling mononuclear phagocyte heterogeneity
  Geissmann F Gordon S Hume DA Mowat AM Randolph GJ - Nat Rev Immunol 10(6):453 (2010)
  When Ralph Steinman and Zanvil Cohn first described dendritic cells (DCs) in 1973 it took many years to convince the immunology community that these cells were truly distinct from macrophages. Almost four decades later, the DC is regarded as the key initiator of adaptive immune responses; however, distinguishing DCs from macrophages still leads to confusion and debate in the field. Here, Nature Reviews Immunology asks five experts to discuss the issue of heterogeneity in the mononuclear phagocyte system and to give their opinion on the importance of defining these cells for future research.
• Corrigendum: Exploring the full spectrum of macrophage activation
  - Nat Rev Immunol 10(6):460 (2010)
  The authors would like to include as an addendum the contribution of R. Stout and J. Suttles to the conceptual framework of macrophage plasticity that was mentioned in our Review. Their ideas on the ability of macrophages to change their functional phenotype in response to their tissue environment were previously published in two review articles (J. Leuk. Biol. 76, 509–513 (2004) and Immunol. Rev. 206, 60–71 (2005)).