Volume 20 Issue 2, February 2019

Activation of STING requires its translocation from the endoplasmic reticulum (ER) through the Golgi to vesicles, but the mechanisms that control its localization have been unclear. The ER calcium sensor STIM1 acts as an ER-retention factor that anchors STING on the ER and limits STING signaling.

Innate lymphoid cell–derived cytokine IL-13 promotes the maintenance of intestinal stem cells through stabilization of β-catenin. The circular RNA circPan3 regulates mRNA encoding the cytokine receptor subunit IL-13Rα and downstream IL-13 signaling to stabilize the β-catenin pathway in intestinal stem cells.

The N⁶-methyladenosine (m⁶A) RNA-modification pathway substantially affects the outcome of viral infection. Studies now show that m⁶A modification of transcripts encoding type I interferons limits the duration of anti-viral signaling.

A new target for controlling T cell responses adds to the list of key processes dependent on the synthesis of tetrahydrobiopterin, which is essential for neurotransmitter and nitric-oxide production and pain control.

In this Perspective, Willcox and Willcox discuss the inherent challenges and future possibilities in identifying the ligands recognized by the γδ TCR.

Basophils constitute <1% of peripheral blood leukocytes. Piliponsky and colleagues show that basophils serve as a critical component of antibacterial responses by secreting tumor necrosis factor at early time points after systemic infection.

ELMO1 is a protein centrally involved in controlling the engulfment of apoptotic cells. Ravichandran and colleagues demonstrate a noncanonical role for ELMO1 in the promotion of neutrophil migration and inflammatory arthritis.

STIM1 is a calcium sensor that is essential for functional lymphocyte responses. Gwack and colleagues demonstrate a calcium-independent role for STIM1 in macrophages that regulates their production of type I interferons.

Using scRNA-seq analysis, Bhattacharya and colleagues identify a subset of profibrotic lung macrophages that have a gene expression signature intermediate between those of monocytes and alveolar macrophages.

RNAs can be dynamically modified by N⁶-methylation of adenosine (m⁶A), which leads to their destabilization. Stern-Ginossar and colleagues demonstrate a role for m⁶A modification of host transcripts encoding type I interferons during viral infection.

Fan and colleagues show that circular RNA circPan3 controls expression of the cytokine receptor IL-13Rα1 on intestinal stem cells and, thus, the renewal of those cells in response to IL-13 derived from group 2 innate lymphoid cells.

Farrar and colleagues show that thymic T_reg cells are generated through two distinct developmental programs that are both required for a comprehensive T_reg cell repertoire.

The tumor microenvironment is central to the immunogenicity of tumors. Ho and colleagues show that activity of the mitochondrial protein UCP2 in tumors enhances their immunogenicity through the recruitment of dendritic cells and reprogramming of this microenvironment.

Regulatory T cells suppress target cells through diverse mechanisms. Shevach and colleagues demonstrate that regulatory T cells in vivo strip complexes of cognate peptide and major histocompatibility complex class II from dendritic cells and thereby help to maintain immune homeostasis.

The transcription factor Foxp1 regulates the quiescence of naïve T cells. Rudensky and colleagues show that Foxp1 has a role that is cooperative and synergistic with that of Foxp3 in regulatory T cells, distinct from its roles in conventional CD4⁺ T cells.