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The gut immune system distinguishes commensal from dangerous microbes. Lee and colleagues delineate a pathway that 'fine tunes' the production of microbicidal reactive oxygen species to combat infections efficiently while tolerating commensal microbes.
In vitro studies suggest that the adaptor TANK is needed for the production of type 1 interferon. Using TANK-deficient mice, Akira and colleagues instead find that TANK negatively regulates Toll-like receptor and B cell antigen receptor signaling in vivo.
Expression of peripheral tissue antigens may be important for peripheral T cell tolerance. Fathman and colleagues demonstrate involvement of the transcription factor Deaf1 in maintaining this expression and link a Deaf1 isoform with type 1 diabetes.
B cell antigen receptors containing immunoglobulin G (IgG) or IgE, but not those containing IgM, show enhanced signaling. Wienands and colleagues trace this boosted signaling capacity to conserved IgG and IgE cytoplasmic tyrosine residues that recruit the adaptor Grb2.
In response to some signals, dendritic cells can become tolerogenic. Rabinovich and colleagues show that galectin-1 drives the differentiation of tolerogenic DCs via a circuit involving interleukins 27 and 10.
Patients infected with human immunodeficiency virus (HIV) have profoundly dysfunctional T and B cell populations. Cerutti and colleagues show that HIV-infected macrophages form long-range conduits that deliver the immunosuppressive HIV protein Nef to distal B cells, inhibiting their function.
SAP family adaptors, including SAP, EAT-2 and ERT, individually influence natural killer cell function. Veillette and colleagues show that natural killer cells lacking all three adaptors fail to eliminate unwanted hematopoietic cells.
The polarization of naive CD4+ T cells to become T helper type 2 cells requires the transcription factor GATA-3. Sen and colleagues show that T cell antigen receptor signals induce interleukin 4–independent but TCF-1–β-catenin–dependent early expression of GATA-3.
The stability of expression of the transcription factor Foxp3 in vivo has not been thoroughly assessed. Bluestone and colleagues find that Foxp3 expression can be unstable and that cells that lose Foxp3 expression can assume a proinflammatory autoaggressive phenotype.
Immunity-related GTPase 1 (Irgm1) is needed for defense against bacteria that reside in phagosomes of macrophages. MacMicking and colleagues identify molecular mediators that act 'upstream' and 'downstream' of Irgm1 in the phagosomal membrane.
After binding double-stranded RNA, RIG-I induces production of type 1 interferon. Hornung and colleagues find that RIG-I detects viral DNA via double-stranded RNA intermediates generated by RNA polymerase III.
The molecular mechanisms that underpin thymocyte selection remain incompletely defined. Groups led by Love, Gascoigne and Schwartz independently identify Themis, a signaling protein essential for the positive selection of thymocytes.
Apoptosis of Mycobacterium tuberculosis (Mtb)-infected macrophages restricts the spread of infection. Basu and colleagues delineate the signaling pathway needed for death of Mtb-infected cells.
The molecular mechanisms that underpin thymocyte selection remain incompletely defined. Groups led by Love, Gascoigne and Schwartz independently identify Themis, a signaling protein essential for the positive selection of thymocytes.
The molecular mechanisms that underpin thymocyte selection remain incompletely defined. Groups led by Love, Gascoigne and Schwartz independently identify Themis, a signaling protein essential for the positive selection of thymocytes.
Helper T cells become polarized to effect a 'division of labor'. Sallusto and Spits and colleagues identify a new subset of skin-homing helper T cells, TH-22 cells, that secrete interleukin 22.
Helper T cells become polarized to effect a 'division of labor'. Sallusto and Spits and colleagues identify a new subset of skin-homing helper T cells, TH-22 cells, that secrete interleukin 22.
Tonic antigen receptor signaling contributes to the homeostasis of naive lymphocytes. Alarcón and colleagues show that resting lymphocytes transmit tonic antigen receptor signals through the GTPase TC21 to trigger the PI(3)K pathway.
Mature B cells express immunoglobulin D, but its function is unknown. Cerutti and colleagues show that respiratory mucosal B cells secrete immunoglobulin D, which activates basophils and enhances antimicrobial function.
Macrophages infected with virulent Mycobacterium tuberculosis die by necrosis. Remold and colleagues show that virulent M. tuberculosis promotes necrosis by damaging the plasma membrane and inhibiting its repair.