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The interleukin 17 (IL-17) family includes six cytokines and five receptors. Garcia and co-workers solve the crystal structure of the receptor IL-17RA bound to IL-17F and suggest that IL-17RA may act as a shared subunit among multiple IL-17 receptor complexes.
T cell activation triggers large calcium fluxes. Flavell and colleagues show tonic calcium signaling via Cav1.4-β3 channels are needed for the survival and homeostasis of naive CD8+ T cells.
Polyubiquitin moieties often accumulate on bacteria that colonize the cytoplasm of mammalian cells. Randow and co-workers find that the protein NDP52 recognizes these ubiquitin moieties, and is needed for the control and autophagy of cytoplasmic bacteria.
Bacterial ligands cannot induce Toll-like receptor 2 (TLR2)-dependent production of type I interferon. Barton and colleagues find that, in contrast, viral ligands trigger TLR2-dependent interferon production by a subset of inflammatory monocytes.
Endogenous peptides that positively select major histocompatibility complex class II-restricted T cell receptors have not yet been identified. Groups led by Davis and Allen identify several such peptides and find that they influence activation and homeostasis of peripheral T cells.
Endogenous peptides that positively select major histocompatibility complex class II-restricted T cell receptors have not yet been identified. Groups led by Davis and Allen identify several such peptides and find that they influence activation and homeostasis of peripheral T cells.
The inhibitory protein PD-1 is expressed on activated T cells. Fife and colleagues find that interactions between PD-1 and its ligand PD-1L are needed to maintain tolerance and prevent interactions between tolerized T cells and dendritic cells.
Interleukin 10–deficient mice develop spontaneous colitis. Kronenberg and colleagues find that interleukin 10 released by myeloid cells in the intestine is needed to maintain expression of the transcription factor Foxp3 in regulatory T cells.
Embryonic lymph node formation requires lymphoid tissue–inducer cells. Mebius and colleagues show that neurons adjacent to lymph anlagen synthesize retinoic acid, which triggers expression of the chemokine CXCL13 needed for the initial attraction of lymphoid tissue–inducer cells.
The precise mechanisms by which the adaptor CARD9 facilitates resistance to bacterial infection remain unclear. Lin and colleagues document a role for CARD9 in the production of microbicidal reactive oxygen species.
In regulatory T cells, a decrease in expression of the transcription factor Foxp3 results in loss of suppressor function. Rudensky and co-workers find that Runx-CBFβ complexes are essential for maintaining Foxp3 expression in regulatory T cells.
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.
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.
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.
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 TH-17 cells to the list of T cell subsets enriched by self-reactivity.
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.
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.
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 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.
The mediators that drive the progressive phase of multiple sclerosis remain undefined. Weiner and colleagues find that 15α-hydroxycholestene is expressed abundantly only during progressive multiple sclerosis and activates macrophages, microglia and astrocytes via poly(ADP-ribose) polymerase 1.