Volume 9 Issue 7, July 2008

A vibrant and eclectic international immunology meeting recently took place in the Arabian Desert of the United Arab Emirates, in the heart of the Islamic world.

This report presents themes highlighted during the eclectic and stimulating Metchnikoff's Legacy in 2008 meeting hosted at the Institut Pasteur in April 2008 in honor of the 100^th anniversary of the 1908 Nobel Prize.

Increasing evidence suggests that immune mechanisms underlie major inflammatory diseases that show no overt microbial etiology. In this context, a 4-day conference of clinical and nonclinical scientists convened in the United Arab Emirates to consider recent research developments in this fast-moving field.

CIITA encodes the 'master regulator' of the expression of major histocompatibility complex class II genes. A new layer of complexity has been identified in the control of CIITA expression, which involves the formation of a complex three-dimensional chromatin structure promoted by interactions among many distant regulatory elements.

Transcription factors of the Ets family are important for mammalian development. A genetic screen now finds that the Ets family member Erg is essential for definitive hematopoiesis and adult hematopoietic stem cell function.

Neutrophils can respond to many chemotactic signals, but how these cells 'prioritize' such signals to react to invading pathogens has remained unclear. The phosphatase PTEN seems to be critical in directing the migration of neutrophils toward their end target in a complex milieu of competing signals.

The mechanisms responsible for establishing allelic exclusion remain enigmatic. New data indicate that stochastic interactions of antigen-receptor alleles with repressive nuclear compartments may contribute to the mechanisms that support allelic exclusion.

Additional immune functions of basophils have been identified in recent years. Mack and colleagues add to this growing list by showing that basophils enhance humoral memory responses by producing interleukins 4 and 6 in response to specific antigen.

Basophils are associated mainly with allergy and immune responses to parasites. Mack and colleagues now show that 'antigen-specific' basophils contribute to the humoral memory response by supplying interleukins 4 and 6.

Leukocytes sense and move in the direction of chemoattractants. Kubes and colleagues show that the phosphatase PTEN is required by migrating neutrophils to 'prioritize' multiple chemoattractant signals, as are encountered in infected tissues.

Complement 5 (C5) generates the C5a anaphylatoxin and C5b, a component of the membrane attack complex. Andersen and colleagues present the crystal structure of C5 and identify similarities and differences between C5 and other complement proteins.

Mechanisms facilitating Toll-like receptor 2 (TLR2) ligand recognition are incompletely understood. De Diego and colleagues show that integrin β₃ and the serum protein vitronectin are essential for responsiveness to a panel of TLR2 agonists.

The characteristics of the cell type(s) responsible for initiating protective gut immune responses are not fully defined. Akira and colleagues show that TLR5⁺ lamina propria dendritic cells trigger, in a retinoic-dependent way, the production of interleukin 17 and immunoglobulin A.

The molecular basis of ligand recognition by γδ TCRs remains vague. Adams and colleagues show that the CDR3δ loop, when grafted in place of a CDR3α loop, is sufficient to confer γδ TCR specificity on an αβ TCR.

The transcription factor CIITA regulates coordinated MHC class II gene expression. Bremner and colleagues show that the chromatin-remodeling protein BRG1 confers interferon-γ responsiveness on the CIITA locus by inducing the formation of chromatin loops.

Developing thymocytes carry out precise assembly of D-to-J followed by V-to-DJ rearrangements at the Tcrb locus. Liu and colleagues show that the transcription factor Fos directs ordered temporal recombination of D segments.

The influence of repressive nuclear compartments on Tcrb rearrangement remains uncertain. Krangel and colleagues show that frequent stochastic, rather than directed, association of Tcrb alleles with repressive compartments promotes monoallelic recombination at this locus.

Ets family transcription factors function in mammalian development. Kile and colleagues demonstrate that the Ets family member Erg is essential for definitive hematopoiesis and adult hematopoietic stem cell function.