Volume 10 Issue 5, May 2009

Do you delight in Brahms? Do you delight in immunology? Tada Taniguchi recounts the story of Type 1 interferon and its downstream regulators.

How the immune system responds to local infection and establishes protective immunity in susceptible tissues remains unclear. Two new studies show that local tissue-resident dendritic cells prime cytotoxic T lymphocyte responses and that memory cytotoxic T lymphocytes remain in the tissue to provide antiviral immunity.

Little is known about how pathogenic T cells gain access to the uninflamed brain in multiple sclerosis and experimental autoimmune encephalomyelitis. A new study reports that interleukin 17–producing T helper cells enter the uninflamed central nervous system through the choroid plexus by a CCR6-CCL20–dependent mechanism.

The 3020insC mutation in Nod2 is associated with Crohn's disease, but how it influences disease pathogenesis is unknown. A new study shows that the 3020insC mutant protein fails to activate a key transcription factor that drives interleukin 10 expression, resulting in reduced production of this anti-inflammatory cytokine.

T cell expansion and contraction during the immune response to pathogens are regulated by a wide variety of cell-intrinsic and cell-extrinsic factors. A new study identifies a role for CTLA-4 signaling and activation of the Foxo3 transcription factor in modulating T cell populations.

Several NOD2 mutations are associated with a greater risk of Crohn's disease. Ma and colleagues show that the 3020insC Nod2 mutant actively suppresses IL10 transcription by interfering with phosphorylation of the nuclear ribonucleoprotein hRNP-A1.

MHC class I presentation of viral peptides aids CD8⁺ T cell recognition of infected cells. Desjardins and colleagues describe an MHC class I viral peptide presentation pathway that integrates autophagosomes and proteasome-dependent processes.

The functions of individual dendritic cell subsets in the skin are unclear. Heath and colleagues now show that langerin-positive CD103⁺ dermal dendritic cells are the main migratory subtype able to cross-present antigen.

Inhaled allergens induce many changes in airway function. Kheradmand and colleagues show that matrix metalloproteinase 7 activates the cytokine interleukin 25 and inhibits retinoic acid–mediated induction of regulatory T cells, thereby heightening allergic responses.

Foxo transcription factors influence a wide variety of cellular responses. Hedrick and colleagues show that dendritic cells express Foxo3 to suppress the production of interleukin 6 and prevent excessive accumulation of antigen-specific T cells.

Whether T_H1 or T_H-17 cells initiate experimental autoimmune encephalomyelitis is unclear. Sallusto and colleagues now show that CCR6⁺ T_H-17 lymphocytes initiate it by entering the brain through the choroid plexus.

The relationship between peripheral and recirculating memory cells remains mostly undefined. Carbone and colleagues present evidence of tissue-resident memory T cells that can provide protective immunity at points of pathogen entry.

T cell antigen receptor signaling occurs in microclusters that coalesce into immune synapses. Bretscher and colleagues show that myosin IIA is required for directed microcluster movement and sustained T cell antigen receptor signaling.

The cytidine deaminase AID is required for antibody gene diversification. Casali and colleagues show that the transcription factor HoxC4 is expressed in germinal centers and is required for AID expression.