Volume 18 Issue 11, November 2017

By switching its partners, FoxP3 segregates into functional and non-functional transcriptional complexes.

A new and unexpected role is identified for Srebps in controlling NK cell activity that is independent of their role in lipid biosynthesis.

The differentiation of follicular regulatory T cells can be limited by the cytokine IL-2, preventing the emergence of autoantibodies. This research identifies these cells as key regulators of the germinal center response.

Dysfunctional immunity is associated with dengue hemorrhagic fever and dengue shock syndrome. Structural analyses reveal that a key germline-encoded contact between the T cell antigen receptor and a peptide underpins the immunodominance of dengue-virus-specific CD8⁺ T cell responses of weak affinity.

Recent decades have seen an alarming rise in the incidence of autoimmune disease. In a Perspective, Matarese and colleagues discuss the evidence showing that changes in diet and metabolic workload can account for, at least in part, rises in the frequency of autoimmune disease.

NK cells are cytotoxic cells that combat tumors and viral infection. Finlay and colleagues show that the effector function of cytokine-activated NK cells depends on glucose metabolism via the citrate–malate shuttle that requires the metabolic regulator Srebp.

Ganss and colleagues show that targeting the inflammatory cytokine LIGHT to tumor vessels via a vascular targeting peptide induces tertiary lymphoid structures and enables the influx of endogenous T cells and tumor killing.

T cells developing in the thymus are signaled during positive selection to differentiate into either CD4⁺ T cells or CD8⁺ T cells. Singer and colleagues show that CD8⁺-lineage specification is signaled exclusively by cytokines, including cytokines that do not signal via the γ_c receptor, and that these are the only signals in the thymus that upregulate the transcription factor Runx3d to direct specification to the CD8⁺ lineage.

Cross-reactivity to dengue virus serotypes can trigger life-threatening inflammation. Culshaw et al. show that germline-encoded components of dengue-virus-specific TCRs influence antigen engagament and suggest that ‘innate-like’ recognition of the virus might underpin harmful cross-reactivity.

Foxp3 is the T_reg cell lineage–defining transcription factor, but its mechanisms of action are still being elucidated. Benoist and colleagues comprehensively generate Foxp3 mutants to delineate how it functions in a cell-context- and molecular-complex-dependent manner.

Humoral immunity is necessary for controlling viral infection. Ballesteros-Tato and colleagues show that development of follicular regulatory T cells is prevented by high concentrations of interleukin 2 at the peak of viral infection, but resumes at later time points to suppress autoantibody production.

Diamond, Screaton and colleagues show that certain cross-reactive neutralizing antibodies to dengue virus have therapeutic activity against Zika virus infection in immune-privileged sites in vivo.