Image depicting the four cardinal signs of inflammation - redness, heat, swelling and pain - originally described by the Roman Aulus Cornelius Celsus in the first century AD. This month we focus on how inflammation is resolved in a series of specially commissioned review articles. These articles and additional features are available free online (www.nature.com.ni/focus/inflammation/index.html) during December 2005. Artwork by Lewis Long.

L-selectin interacts with specialized glycans on high endothelial venules. Fukuda and colleagues (p 1096) and Rosen and colleagues (p 1105) report two sulfotransferases that function cooperatively to add sulfate esters to specific sugar residues on glycans are essential for L-selectin-mediated lymphocyte homing. The image depicts L-selectin binding (red) and expression of one sulfotransferase (green) on high endothelial venules. See also News and Views by McEver (p 1067). Original fluorescence micrograph by Hiroto Kawashima. Art work by Lewis Long.

During dendritic cell maturation surface expression of peptideãƒâƒã‚âƒãƒâ‚ã‚â‚ãƒâƒã‚â‚ãƒâ‚ã‚â–major histocompatibility complex MHC) is enhanced. Strominger and colleagues (p 1020; News and Views by Jensen, p 968) find that inhibition of caspasemediated cleavage of adaptor protein 1 is required for appropriate sorting of molecules such as MHC class II in the cells. The image shows surface expression of peptideãƒâƒã‚âƒãƒâ‚ã‚â‚ãƒâƒã‚â‚ãƒâ‚ã‚â–MHC class II (black dots) on a dendritic cell (red) after treatment with a caspase inhibitor. Electron microscopy by Laura Santambrogio and Ilaria Potolicchio. Art work by Lewis Long.

Notch signaling is required during β-selection. Ciofani and Zúñiga-Pflücker (p 881) demonstrate that Notch signaling regulates cellular metabolism, allowing the energy-intensive outcomes of β-selection to occur. The image depicts a coculture of preT cells (purple) and OP9-DL1 cells expressing the Notch ligand Delta-like 1. Confocal microscopy by Thomas M. Schmitt. Art work by Lewis Long.

CD1d presents endogenous and exogenous lipid antigens to natural killer T cells. Wilson, Teyton and colleagues (p 810) and Jones, Cerundolo and colleagues (p 819) have solved the crystal structures of mouse and human CD1d, respectively, in complex with an agonist ligand. The image depicts a cross-sectional view of the structure and shows snug positioning of the α -galactosylceramide ligand in the grooves of CD1d. See also News and Views by Godfrey and Rossjohn (p 754). Artwork by Lewis Long (adapted from an image by Robert Esnouf).

Nature Immunology celebrates its fifth anniversary this month. To mark this occasion, we have assembled a collection of landmark papers from our pages that highlight the broad subject area covered by Nature Immunology in the past 5 years. This content is free online (http://www.nature.com/ni/focus/birthday/index.html) during July. Artwork by Lewis Long.

TCR engagement activates multiple signaling pathways. Weiss and colleagues (p 608) show optimal T cell activation requires recruitment of the kinase PAK1 to the immune synapse and is depicted here as a color gradient (blue through red). The original image (by Hyewon Phee) is a Z-stack composite of PAK1 fluorescence at the immune synapse; not shown is the antigen presenting cell. Artwork by Lewis Long.

Integrin activation is key for leukocyte exit from the bloodstream. Shamri et al. (p.497) show that the nature of the chemokine signal critically influences leukocyte arrest under flow conditions (see also News and Views by Laudanna, p.429). The image represents a multiphoton intravital micrograph depicting T cells (green) and dendritic cells (red) in the vicinity of a high endothelial venule (yellow). Micrograph by Thorsten Mempel and Ulrich von Adrian. Artwork by Lewis Long.

The 'yin-yang' icon is a symbol of balance and harmony between two opposing forces. These forces are pervasive in our immune system, where the balance between regulatory T cells and reactive cells is important in maintaining homeostasis. This month we focus on the biology and function of regulatory T cells with a series of specially commissioned articles. The content and additional features are free online (www.nature.com/ni/focus/regulatory_tcells) during April 2005. Cover by Lewis Long.

Airborne pollution from motor vehicles and industries is a serious threat to human health. Starting from this month and throughout 2005, Nature Immunology examines the contribution of the environment and our modern lifestyle to the increasing prevalence of allergy. In this issue, Saxon and Diaz-Sanchez (p.223) discuss the potential effects of pollution. Artwork by Lewis Long.

Positive selection of thymocytes requires calcium signaling. Lewis and colleagues (p 143; News and Views by Cahalan, p 126) simultaneously visualized thymocyte motility and internal Ca2+ concentration ([Ca2+],) by two-photon microscopy. A single thymocyte's migration in a thymus slice is shown. 'Cooler' colors indicate the low [Ca2+], of rapidly migrating thymocytes, whereas 'hotter' colors indicate increased [Ca2+], and thymocyte immobility. Thus, Ca2+ signals serve as a stop signal during positive selection. Art work by Lewis Long.

Unlike other loci, only one allele of the immunoglobulin genes in a B cell is used to produce antibodies. Skok and colleagues (p 31) investigate how such 'allelic exclusion' is enforced. The Igh genes temporarily contract, which juxtaposes distal VH segments with downstream DHJH sequences. Signaling through the pre-BCR triggers loss of this close apposition, precluding further rearrangements with distal VH regions. Confocal image shows in situ nuclear hybridization signals of the looped Igh locus. Artwork by Lewis Long.