Volume 10 Issue 10, October 2009

More than 20 years after the first successful engraftment of human leukocytes and hematopoietic organs in mice, scientists met for the 2nd International Workshop on Humanized Mice to discuss progress and to highlight expectations in this dynamic field.

The Science Gallery, Trinity College Dublin, recently held an exhibition called “INFECTIOUS: STAY AWAY” that used art to illustrate infection and immunity. Luke O'Neill talks to one of the artists, Gordana Novakovic, about her involvement in this project.

Agonist encounter can divert thymocytes into several unconventional T cell subsets, many of which exhibit regulatory properties. Unexpected findings indicate that agonist selection can drive the differentiation of interleukin 17–producing cells in the thymus.

Cytosolic DNA sensors have remained poorly defined so far. Two recent studies identify a previously undefined cytosolic DNA-sensing pathway that depends on the RNA polymerase III–mediated conversion of microbial DNA into 5′-triphosphate double-stranded RNA that activates the RNA helicase RIG-I.

Transcription factors are critical regulators of cell fate in the hemato-lymphoid system. New evidence indicates that the basic leucine zipper transcription factor E4BP4 (also known as NFIL3) is essential for natural killer cell specification.

Nod2 is a cytoplasmic Nod-like receptor protein that detects the peptidoglycan subfragment muramyl dipeptide. New work shows that Nod2 also has an important role in recognizing viruses and in triggering interferon production during viral infection.

After binding double-stranded RNA, RIG-I induces production of type 1 interferon. Hornung and colleagues find that RIG-I detects viral DNA via double-stranded RNA intermediates generated by RNA polymerase III.

The intracellular 'biosensor' Nod2 responds to bacterial peptidoglycan by inducing activation of the transcription factor NF-κB. Bose and colleagues now find that Nod2 can also function as a cytoplasmic viral pattern-recognition receptor.

Different pathogens induce different cytokine production via the C-type lectin DC-SIGN. Geijtenbeek and colleagues show that distinct carbohydrates on the pathogen surface induce the assembly and use of distinct DC-SIGN signaling complexes.

The role of Pellino proteins in Toll-like receptor (TLR) signaling is not completely understood. Sun and colleagues now find that Pellino1 ubiquitinates the signaling molecule RIP1 and is essential for TRIF-dependent TLR signal transduction in mice.

Celiac disease is associated with HLA-DQ2.5 expression. Sollid and colleagues identify why this association exists by showing that binding of peptide to HLA-DQ2.5 is kinetically more stable.

Antibody-secreting cells switch expression of membrane-bound B cell antigen receptors to soluble immunoglobulin production by alternative mRNA polyadenylation. Milcarek and colleagues show that ELL2 and CstF-64 associate with RNA polymerase II to enhance promoter-proximal polyadenylation and immunoglobulin secretion.

How signals through the pre–B cell antigen receptor (pre-BCR) and IL-7 receptor (IL-7R) coordinate population expansion of pre-B cells with subsequent recombination of the immunoglobulin κ-chain locus is unclear. Clark and colleagues show that pre-BCR signaling via the Ras-MEK-Erk pathway poises pre–B cells to undergo differentiation after escaping IL-7R signaling.

Little is known about the transcription factors that facilitate NK cell differentiation. Brady and colleagues find that the basic leucine zipper transcription factor E4bp4 is essential for NK cell development in mice.

Several unconventional T cell populations, including γδ T cells and regulatory T cells, are selected by recognition of self antigen in the thymus. Craft and colleagues add T_H-17 cells to the list of T cell subsets enriched by self-reactivity.