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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 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.
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.
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.
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.
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.
How immunoglobulin gene loci are specifically targeted by activation-induced cytidine deaminase while the rest of the genome avoids potentially mutagenic events is becoming clearer.
Antibody responses are critical for host protection against many pathogens. By reporting what actually occurs in vivo, two new studies provide important clues about follicular helper T cells that are dedicated to providing help to B cells.
Two papers published recently in Science exploit new transgenic mouse systems to explore the path that activated CD8+ T cells take on the way to memory differentiation.
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.
Whether TH1 or TH-17 cells initiate experimental autoimmune encephalomyelitis is unclear. Sallusto and colleagues now show that CCR6+ TH-17 lymphocytes initiate it by entering the brain through the choroid plexus.
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.