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Foxp3 is the Treg 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.
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.
Helicases are vital to the induction of antiviral responses. Cao and colleagues demonstrate that the helicase DDX46 is involved in the epigenetic regulation of select RNA species encoding antiviral molecules, which leads to the retention of the RNAs in the nucleus and thus blockade of their translation and the activity of the proteins encoded.
Targeting the transcription factor RORγt in autoimmunity could disrupt thymocyte development and lead to thymic lymphoma. Sun and colleagues identify a two-amino-acid substitution in RORγt that ‘preferentially’ disrupts TH17 differentiation, not thymocyte development.
The effect of the cytokine IFN-λ in non-epithelial cells remains unclear. Zanoni and colleagues show that IFN-λ specifically activates a signaling pathway that diminishes the production of reactive oxygen species and degranulation in neutrophils.
Poor glycolysis and increased fatty-acid synthesis feed the locomotion machinery in T cells from people with rheumatoid arthritis and allow these cells to enter the synovium and propagate joint inflammation and destruction.
The ability to expand and contract populations of myeloid and lymphoid cells during emergency hematopoiesis helps shape the immune response. The expression of intracellular and soluble forms of osteopontin regulates apoptosis thresholds differently in myeloid cells and lymphoid cells to counter infection.
The histone lysine methyltransferase MLL4 primes the locus encoding the transcription factor Foxp3 for transcriptional activation in thymus-derived and inducible regulatory T cells.
The cytokine TGF-β allows tumors to evade the immune system by converting conventional natural killer cells into type 1 innate lymphoid cells devoid of cytotoxic function.
Long non-coding RNAs (lncRNAs) are being increasingly appreciated as important regulators of gene expression. Chang and colleagues review the roles identified for lncRNAs in the immune system and discuss models for how lncRNAs mediate their effects.
The molecular events that initiate lymphoid-lineage specification remain unidentified. Cumano and colleagues define the transcriptional signatures that characterize the loss of B cell or T cell potential.
No response by an immune cell occurs in isolation but is instead the summation of multiple interacting signals. Ivashkiv and colleagues describe the epigenetic landscape that results from the integration of the inflammatory cytokines type I interferons and TNF.
Lazarevic and colleagues show that T-bet-dependent NKp46+ innate lymphoid cells reside within the meninges of the CNS and initiate meningeal inflammation, thereby facilitating T cell entry into parenchymal CNS tissues and contributing to neuroinflammation.