Volume 17 Issue 4, April 2016

The detection of cytosolic DNA by the sensor cGAS triggers potent antiviral responses. New data now propose that cGAS is regulated on a post-translational level by glutamylation.

The accumulation of intestinal Foxp3⁺ regulatory T cells (T_reg cells) in response to the microbiota is tightly regulated. Epithelial apoptosis inhibits the production of tolerogenic interferon-β by myeloid cells and thereby reduces the frequency of T_reg cells and lowers the threshold for inflammatory responses.

Single-cell RNA sequencing of human innate lymphoid cells (ILCs) reveals conserved transcriptional programs and defines previously unappreciated heterogeneity. These findings pave the way for future investigation of the function and therapeutic potential of ILCs in human health and disease.

The silencing of autoreactive immature B cells is regulated by the binding of self antigens to B cell antigen receptors. New findings show that microRNAs control mechanisms of B cell tolerance.

Control of infection depends on the efficient coordination of responses by various cell populations of the immune system. Gause and colleagues review the interactions between cells of the innate immune system and stroma that enable effective responses to invading pathogens.

In this Perspective, Chang and Pearce discuss recent progress in understanding how metabolic pathways control T cell function and how these pathways can be manipulated for therapeutic purposes.

cGAS is an important sensor of cytosolic DNA, but the mechanisms that regulate it remain largely unknown. Fan and colleagues demonstrate that cGAS and its DNA-binding activities are negatively regulated by glutamylation.

Van Heijst and colleagues show that CD4⁺ T cells are programmed to downregulate TCR expression at the peak of clonal expansion in proportion to the strength of initial antigen recognition.

Activation of NK cells by hematopoietic targets is controlled by the SLAM receptors and SAP adaptors. Veillette and colleagues show that SLAM-SAP pathways also control NK cell cytotoxicity against nonhematopoietic targets through SLAMF6 homotypic interactions and education.

Type I interferons suppress viral infection. Ge and colleagues show that the kinase CK1ɛ contributes to this innate immune response by phosphorylating the signaling adaptor TRAF3 to facilitate the expression of type I interferons.

Sepsis is poorly understood, largely untreatable and frequently fatal. Netea and colleagues assess both mouse sepsis and human sepsis to demonstrate that its late phase is characterized by immunoparalysis and broad metabolic alterations in cells of the immune system.

The cytokine TGF-β maintains the residency of cells of the immune system in barrier tissues. Kaplan and colleagues demonstrate that specific integrins expressed by epithelial cells activate latent TGF-β and that this is critical to maintain residency of cells of the immune system in the skin and gut.

Using genetic approaches and transcriptional profiling, Kallies and colleagues reveal a common program of effector CD8⁺ T cell differentiation that is regulated by the cooperation of IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet.

Immature self-reactive B cells undergo central tolerance as they emerge from the bone marrow. Xiao and colleagues show that B cell tolerance requires downregulation of the microRNA miR-148a, as aberrant expression of miR-148a increases survival of autoreactive B cells and contributes to autoimmunity.

Epithelia continually undergo apoptosis, but the physiological importance of this is unclear. Shibuya and colleagues show that apoptotic epithelial cells bind the glycoprotein CD300a on a dendritic cell subset at barrier surfaces and this negatively regulates commensal-driven T_reg cell proliferation.

Several populations of innate lymphoid cells have been identified by their cytokine and transcription factor expression. Mjösberg and colleagues report considerable heterogeneity within human tonsil innate lymphoid cell subpopulations, as revealed by single-cell RNA-sequencing profiling.

Using a systems-biology approach, Liston and colleagues profile the immune system of 670 healthy volunteers to provide a description of the population-level heterogeneity in the cellular composition of the circulating immune system.