Volume 11 Issue 11, November 2010

Complexities in sample handling, instrument setup and data analysis are barriers to the effective use of flow cytometry to monitor immunological parameters in clinical trials. The novel use of a central laboratory may help mitigate these issues.

Human immunodeficiency virus type 1 (HIV-1) seems to avoid detection by nucleic acid sensors. This is probably due to the host exonuclease TREX1, which degrades HIV DNA generated during HIV-1 infection.

Neutrophils can function as chief effector cells in inflammation but can also regulate excessive inflammatory responses by secreting anti-inflammatory cytokines. The acute-phase reactant SAA-1 seems to be pivotal in the control of such plasticity.

Induction of the microRNA miR-182 by interleukin 2 in helper T lymphocytes targets the transcription factor Foxo1 and promotes clonal expansion. Targeting this process opens new possibilities for adjuvancy, immunosuppression and anti-inflammatory therapeutics.

Innate immune responses to pathogens are often triggered by nucleic acids, including DNA delivered to the cytoplasm of cells. IFI16 is a newly identified cytoplasmic DNA sensor that induces the transcription of genes involved in the innate response.

Foreign nucleic acids trigger innate immune sensors. Bowie and colleagues identify the PYHIN protein IFI16 as an innate duplex DNA sensor that triggers IFN-β production in a STING-TBK1-IRF3 signaling pathway.

Cells infected with human immunodeficiency virus type 1 do not produce type I interferon responses. Lieberman and colleagues report that the cytosolic exonuclease TREX1 prevents the accumulation of replication intermediates of this virus that could otherwise trigger intracellular sensors.

The function of IL-37 remains elusive. Dinarello and colleagues find that IL-37 acts as a natural suppressor of innate inflammatory and immune responses.

Many activating immunoreceptors are protein complexes in which ligand recognition and signaling functions are provided by separate modules. Wucherpfennig and co-workers report the nuclear magnetic resonance structure of the heterotrimeric DAP12-NKG2C receptor.

IL-12 is believed to mediate antitumor activity via NK and T_H1 cells. However, Becher and co-workers now show that IL-12 activates NKp46⁺ lymphoid tissue–inducer cells, which locally modify the tumor environment.

How neutrophils differentiate into anti-inflammatory or proinflammatory effector cells is unclear. Cerundolo and colleagues now show that systemic serum amyloid A 1 controls the plasticity of neutrophil differentiation.

TGF-β signaling can promote the induction of regulatory T cells. Chi and colleagues show that the sphingosine 1-phosphate receptor S1P₁ inhibits prolonged activity of the signal transducer Smad3 to block the generation of induced regulatory T cells, promoting T_H1 differentiation instead.

Clonal expansion of helper T lymphocytes initially requires inactivation of the transcription factor Foxo1 by post-translational modifications. Mashreghi and colleagues now show in the late phase of clonal expansion, Foxo1 is inhibited post-transcriptionally by the microRNA miR-182.

Since the establishment of the TH1-TH2 paradigm, many other types of specialized T helper cells, including TH17 and regulatory T cells, have been identified. A Nature Collection highlights some seminal research in this fast-paced field.