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Single-cell transcriptome analysis has identified progenitor populations with mast-cell and eosinophil potential that are distinct from the neutrophil-monocyte lineage, segregate early in hematopoietic development and can be discriminated by expression of the transcription factor GATA-1.
Nutrient transport is regulated by signaling pathways that together indicate metabolic checkpoints in T cell self-renewal, differentiation and proliferation.
Whole-body metabolism can affect immune-cell function and vice versa. Turka and colleagues review the unique metabolic properties of Treg cells and how this relates to their function and the outcome of immune responses.
Chronic viral infections are characterized by ongoing inflammation and a dysfunctional T cell response, which results in a failure of the host to clear the pathogen. Now these two hallmarks of infection have been linked by the classic pro-inflammatory cytokine tumor-necrosis factor.
Regulatory T cells must limit activation of the metabolic checkpoint kinase mTOR to maintain their identity. The lipid ceramide serves a unique role in this process by inducing phosphatase PP2A–mediated inhibition of the mTORC1 complex.
Studies using genetic tools have identified the distinct dendritic cell subsets that ensure tolerance to oral antigens in the antigen-rich environment of the gut and suggest a 'division of labor' for protective immunity.
Patients with XLPDR are found to carry an intronic hypomorphic mutation in the gene encoding the catalytic subunit of DNA polymerase-α. Patients' cells display low levels of cytoplasmic RNA:DNA hybrids, which increases the expression of interferon-α-induced genes, a hallmark of monogenic 'type I interferonopathies'.
Bedoui and colleagues discuss the naive state of conventional T cells as an actively repressed condition that supports T cell diversity and enables the flexible differentiation of effectors, and also offers a relevant discrimination criterion between innate and adaptive lymphocytes.
In this Perspective, MacMicking and colleagues discuss the roles of interferon-induced guanylate-binding proteins in directing inflammasome responses and their effects on immunity to a wide variety of microbial pathogens.
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 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 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.
The accumulation of intestinal Foxp3+ regulatory T cells (Treg 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 Treg cells and lowers the threshold for inflammatory responses.
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.
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.
SHARPIN acts independently of the ubiquitin-assembly complex LUBAC to attenuate proximal signaling downstream of TCRs by inhibiting the interaction of Zap70 with the TCRζ chain through Lys63 (K63)-linked polyubiquitination. SHARPIN deficiency enhanced TCR signaling and impaired the development and function of Treg cells.
The NLRP3 inflammasome has broad biomedical relevance, but its activation mechanisms are incompletely understood. NEK7, a kinase that regulates microtubules during mitosis, is identified as a critical and selective upstream regulator of NLRP3 inflammasome activation.
The production of interleukin 12 (IL-12) and IL-23 in dendritic cells is strictly regulated via epigenetic silencing. This transcriptional repression is overcome with the help of the deubiquitinase Trabid and has functional implications in a mouse model of multiple sclerosis.
An important new function for the phosphatase PTEN in regulating interferon responses to viral infection has been delineated. This finding could help explain the remarkable cancer selectivity of many oncolytic viruses.
