Volume 12 Issue 1, January 2011

The fields of immunology, microbiology, nutrition and metabolism are rapidly converging. Here we expand on a diet-microbiota model as the basis for the greater incidence of asthma and autoimmunity in developed countries.

ZAPS, a member of the poly(ADP-ribose) polymerase family, modulates innate antiviral immunity by boosting signaling of the RNA helicase RIG-I.

NF-κB is a critical transcription factor that is regulated by several post-transcriptional modifications. The characterization of their roles would help in the design of new therapeutic targets in cancer and inflammation.

The molecular mechanisms that control T_reg and T_H17 development and the precise role of TGF-β in this process are complex and imperfectly understood. New findings indicate that the helix-loop-helix proteins E2A and Id3 are also critically involved in some of these processes.

T_H2 cells control immune responses to helminth infection and contribute to the development of allergic asthma. A single intronic enhancer element in Il4 can regulate T_H2 differentiation and susceptibility to allergic asthma via interaction with the transcription factor GATA-3.

A family of innate lymphoid cells exist that is capable of rapid cytokine production. Spits and Di Santo review the developmental relationships and physiologic function of this expanding family.

Binding of the transcription factor NF-κB subunit RelA activates proinflammatory gene expression. Gozani and colleagues show that basal expression of RelA target genes is suppressed by methylation of RelA by SETD6, which triggers repressive histone methylation by GLP.

Poly(ADP-ribose) polymerases participate in many biological and pathological processes. Takaoka and co-workers show that the short isoform of PARP-13 (ZAPS) is selectively induced by 5'-triphosphate–modified RNA and regulates signaling mediated by the RNA helicase RIG-I.

Peptides presented to cytotoxic T lymphocytes are typically generated by proteasome action. Kessler and colleagues show that the cytosolic endopeptidases nardilysin and thimet oligopeptidase generate the C termini of tumor-relevant epitopes.

HLA-DM activity ensures that only high-affinity peptides are displayed on MHC class II molecules. Wucherpfennig and colleagues show that interaction of HLA-DR with the N terminus of bound peptides determines susceptibility to HLA-DM.

Immunoglobulin genes are prominent targets of the deaminase AID. Casellas and Nussenzweig and co-workers show that whereas stalled polymerases recruit AID across the B cell genome, efficient hypermutation is restricted to immunoglobulin loci by the RPA cofactor of AID.

Immunoglobulin genes are further diversified by the cytidine deaminase AID. Gearhart and colleagues show immunoglobulin genes accumulate AID-dependent uracil residues within the first 24 hours of B cell stimulation.

The molecular basis of T_H2 lineage commitment is poorly understood. Kubo and colleagues identify the Il4 enhancer HS2 as a target of the transcription factor GATA-3 and show it to be critical for IL-4 production and T_H2 functional commitment.

TGF-β and Foxp3 are required for the development of regulatory T cells. Chen and colleagues show that the helix-loop-helix proteins E2A and Id3 enhance Foxp3 expression and relieve it from inhibition by other transcription factors.

Transcription factors specific for helper T cell lineages, such as T-bet, counter-regulate helper T cell development, but the details of this remain unclear. Glimcher and colleagues unravel the molecular basis of the regulation of T_H17 cells by T-bet.