Hot off the presses! Apr 01 Nat Rev Immunol

The Apr 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:

• 
  - Nat Rev Immunol 11(4):231 (2011)
  
• Mucosal immunology: Steps for keeping calm | PDF (135 KB)
  - Nat Rev Immunol 11(4):233 (2011)
  The development of oral tolerance is important for preventing potentially harmful immune responses against food antigens and commensal organisms. Previous work has shown that in response to fed antigen, dendritic cells (DCs) in the mesenteric lymph nodes (MLNs) induce regulatory T (TReg) cells that actively maintain tolerance.
• Vaccines: Dual TLR hit for vaccine success | PDF (126 KB)
  - Nat Rev Immunol 11(4):234 (2011)
  The induction of persistent antibody responses (that ideally last a lifetime) is a gold standard for most vaccines. But how can this be achieved with recombinant proteins that are poorly immunogenic?
• Antibody responses: FcRn — not just for the kids | PDF (118 KB)
  - Nat Rev Immunol 11(4):234 (2011)
  IgG is the predominant antibody isotype found in the female genital tract and serves as an important defence mechanism against genital tract infections. In a recent study, Zili et al.
• Neuroimmunology | Viral immunity | Inflammation | PDF (89 KB)
  - Nat Rev Immunol 11(4):234 (2011)
  Caspase signalling controls microglia activation and neurotoxicity Burguillos, M. A.et al. Nature9 Mar 2011 (doi:10.1038/nature09788)
• Tumour immunology: TSLP drives human tumour progression | PDF (139 KB)
  - Nat Rev Immunol 11(4):235 (2011)
  Chronic inflammation associated with CD4+ T helper 2 (TH2) cell polarization can promote cancer progression. Two independent studies report that thymic stromal lymphopoietin (TSLP) expression in the tumour microenvironment contributes to tumour growth following intratumoural TH2 cell differentiation.
• Tumour immunology: Pro-metastatic TReg cells get RANKed | PDF (188 KB)
  - Nat Rev Immunol 11(4):236 (2011)
  The presence of regulatory T (TReg) cells in breast cancer tumours marks an invasive phenotype and poor prognosis. A study published in Nature shows that, in addition to their immunosuppressive role in antitumoural responses, CD4+ TReg cells contribute to mammary tumour metastasis through the expression of receptor activator of nuclear factor-κB ligand (RANKL; also known as TNFSF11).
• Antiviral immunity: IL-21 comes with age | PDF (179 KB)
  - Nat Rev Immunol 11(4):236 (2011)
  Depending on the age at which an individual becomes infected with human hepatitis B virus (HBV) there are two different immune response patterns. Infection during infancy often results in chronic disease, whereas infection during adulthood usually leads to an acute response and viral clearance.
• T cells: A little help from mTOR's friends | PDF (132 KB)
  - Nat Rev Immunol 11(4):237 (2011)
  The effects of mammalian target of rapamycin (mTOR) signalling on the T helper (TH) cell response depend on the partners with which mTOR associates, according to new research published in Nature Immunology.The kinase mTOR regulates cellular metabolism in response to environmental factors, and many recent studies have shown that this pathway controls the differentiation and function of immune cells in response to the immune microenvironment.
• Genomic views of STAT function in CD4+ T helper cell differentiation
  - Nat Rev Immunol 11(4):239 (2011)
  Signal transducer and activator of transcription (STAT) proteins are well known for their essential roles in transmitting cytokine-mediated signals and specifying T helper (TH) cell differentiation. Recent technological advances have revealed that STAT proteins have broad and complex roles in gene regulation and epigenetic control, including important roles as functional repressors. However, the challenge of how to link signal transduction, nucleosome biology and gene regulation remains. The relevance of tackling this problem is highlighted by genome-wide association studies that link cytokine signalling and STATs to various autoimmune or immune deficiency disorders. Defining exactly how extrinsic signals control the specification and plasticity of TH cells will provide important insights and perhaps therapeutic opportunities in these diseases.
• Recombination centres and the orchestration of V(D)J recombination
  - Nat Rev Immunol 11(4):251 (2011)
  The initiation of V(D)J recombination by the recombination activating gene 1 (RAG1) and RAG2 proteins is carefully orchestrated to ensure that antigen receptor gene assembly occurs in the appropriate cell lineage and in the proper developmental order. Here we review recent advances in our understanding of how DNA binding and cleavage by the RAG proteins are regulated by the chromatin structure and architecture of antigen receptor genes. These advances suggest novel mechanisms for both the targeting and the mistargeting of V(D)J recombination, and have implications for how these events contribute to genome instability and lymphoid malignancy.
• Platelets and the immune continuum
  - Nat Rev Immunol 11(4):264 (2011)
  Platelets are anucleate cells that are crucial mediators of haemostasis. Most immunologists probably don't think about platelets every day, and may even consider these cells to be 'nuisances' in certain in vitro studies. However, it is becoming increasingly clear that platelets have inflammatory functions and can influence both innate and adaptive immune responses. Here, we discuss the mechanisms by which platelets contribute to immunity: these small cells are more immunologically savvy than we once thought.
• Immunity to fungal infections
  - Nat Rev Immunol 11(4):275 (2011)
  Fungal diseases represent an important paradigm in immunology, as they can result from either a lack of recognition by the immune system or overactivation of the inflammatory response. Research in this field is entering an exciting period of transition from studying the molecular and cellular bases of fungal virulence to determining the cellular and molecular mechanisms that maintain immune homeostasis with fungi. The fine line between these two research areas is central to our understanding of tissue homeostasis and its possible breakdown in fungal infections and diseases. Recent insights into immune responses to fungi suggest that functionally distinct mechanisms have evolved to achieve optimal host−fungus interactions in mammals.
• Are senescence and exhaustion intertwined or unrelated processes that compromise immunity?
  - Nat Rev Immunol 11(4):289 (2011)
  Can the immune system be reactivated continuously throughout the lifetime of an organism or is there a finite point at which repeated antigenic challenge leads to the loss of lymphocyte function or the cells themselves or both? Replicative senescence and exhaustion are processes that control T cell proliferative activity and function; however, there is considerable confusion over the relationship between these two intrinsic cellular control mechanisms. In this Opinion article, we compare the molecular regulation of senescence and exhaustion in T cells. Available data suggest that both processes are regulated independently of each other and that it may be safer to block exhaustion than senescence to enhance immunity.