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Irradiation to condition hosts for bone marrow transplantation leads to alterations in intestinal microbiota. Reddy and colleagues demonstrate that these changes result in reduced butyrate production and breakdown of intestinal barrier function.
The receptor tyrosine phosphatase CD45 has an important role in T cell activation. Davis and colleagues resolve the structure of CD45 and provide molecular insights into how it contributes to productive T cell receptor triggering.
Regulatory T cells use a distinct metabolism to exert their regulatory function. Tsokos and colleagues show that the phosphatase PP2A suppresses the metabolic-checkpoint kinase complex mTORC1 in these cells and is necessary for their function. PP2A activity is regulated by the cellular abundance of ceramide via a transcription factor Foxp3–dependent feedback mechanism.
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.
Functional T cell exhaustion occurs during chronic viral infection or in tumor settings. Beyer et al. report that chronic inflammation mediated by the cytokine TNF is responsible for this dysfunction and that blockade of this pathway restores immune system–mediated control of viral infection.
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.
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.
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.
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.
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.
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.
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.
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.
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 Treg cell proliferation.
SHARPIN is a component of the linear-ubiquitin-chain–assembly complex that positively regulates activation of the transcription factor NF-κB. Liu and colleagues show that SHARPIN regulates TCR signaling independently of NF-κB and that its deficiency impairs Treg cell generation.
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.
T cell anergy is a well-established phenomenon, but its physiological role is unclear. Mueller and colleagues demonstrate that anergic self-reactive T cells are present at steady state and that these are predisposed to generate peripheral regulatory T cells.
Regulatory T (Treg) cells have a distinct cellular metabolism compared to effector T cells. Chi and colleagues show that autophagy is required to maintain the functional integrity and metabolic homeostasis of Treg cells in the face of inflammatory environmental cues.
Sun and colleagues show that the deubiquitinase Trabid mediates the TLR-induced deubiqutination and stabilization of the histone demethylase Jmjd2d at the Il12 and Il23 promoters in dendritic cells.
The precise lineage relationship between innate lymphoid cells and lymphoid tissue–inducer cells is poorly understood. Using single-cell transcriptional analysis and cultures of fetal liver precursor cells, Bendelac and colleagues define the divergence of these cells.