Volume 9 Issue 11, November 2008

The Large Hadron Collider exemplifies big, bold science that can bring great breakthroughs and, perhaps equally importantly, inspire the public's sense of purpose and possibility.

The work of epidemiologists before the isolation of human immunodeficiency virus 25 years ago demonstrates the power of the epidemiological method to gain an understanding of disease pathogenesis.

Cancer cells are more resistant to complement-mediated lysis and use this attribute to set up a locally immunosuppressive environment. However, new findings suggest that tumor-driven complement activation can also provide the tumor a growth advantage.

A flurry of studies has suggested the importance of the actin regulator coronin 1A in lymphocyte development. Now, mutants of this regulator are shown to cause immunodeficiency in both mice and humans.

Major histocompatibility complex class II molecules present peptides to CD4⁺ T cells. New findings indicate that conventional and plasmacytoid dendritic cells handle these molecules differently after activation.

Interferon-γ exerts many effects on the immune system. A new report shows that it induces both autophagy and Irgm1, a GTPase that protects activated CD4⁺ T cells from executing autophagy.

Tumors often resist immune-mediated destruction because of the presence of suppressor cells. Lambris and colleagues show that activated complement C5a helps mediate this effect by recruiting myeloid suppressor cells to the tumor microenvironment.

Activation of intracellular signaling pathways can result in MHC binding to and presentation of phosphorylated peptides. Engelhard and colleagues identify a unique phosphorylated peptide–MHC binding mode that allows solvent exposure of phosphorylated residues.

The antigen-presenting abilities of plasmacytoid dendritic cells (DCs) are not well characterized. Villadangos and colleagues show that unlike conventional DCs, plasmacytoid DCs continue to synthesize and degrade MHC class II molecules, and thereby present endogenous viral antigen, after activation.

Plasmacytoid dendritic cells are best known as potent producers of type I interferon. Butcher and colleagues identify a subset of these cells, characterized by CCR9 expression, that can elicit tolerance in the gut.

Succinate is a Krebs cycle intermediate. Carballido and colleagues show that succinate released by necrotic cells also functions as an 'alarmin' by activating dendritic cells that express the succinate receptor GPR91.

Some bacteria evade immune detection in the human respiratory tract. Slevogt and colleagues show that bacterial stimulation of the ITIM-containing CEACAM1 protein initiates signals that suppress TLR2-induced Akt activation and inflammation.

Interferon-γ (IFN-γ) is toxic to cells, yet IFN-γ-producing cells survive. Feng and colleagues show that expression of the GTPase Irgm1 in these cells confers protection against IFN-γ toxicity.

Interleukin 4 (IL-4) drives T helper type 2 differentiation, whereas IL-2 augments Il4 chromatin accessibility. Leonard and colleagues now find that IL-2 also maintains the expression of Il4ra and other genes in T helper type 2–committed cells.

The transcriptional regulation of Il17 expression is not well understood. Strober and colleagues identify conserved noncoding sequences that, by a mechanism dependent on differential binding of Runx1 to RORγt and Foxp3, regulate Il17 expression.

Defective thymic egress in mice is associated with the peripheral T cell deficiency (Ptcd) locus. Cyster and colleagues find that the actin regulator coronin 1A is mutant in Ptcd and in an atypical patient with SCID.