Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Chemokines are important components of the hematopoietic niche. The atypical chemokine receptor 1 (ACKR1), expressed on erythrocyte precursors, regulates myeloid differentiation.
Thymocytes must undergo positive selection to survive and differentiate. This process is regulated by the TCR-sensitive protein CHMPS by preventing Bcl2 oxidation and degradation.
A study of polymorphisms in the sensor IFIH1 exposes the evolutionary trade-off between a robust antiviral type I interferon response and the risk of interferon-mediated inflammation.
The Hippo signaling pathway regulates cellular proliferation and survival during tissue growth and cancer. In CD4+ T cells, members of the Hippo family modulate autoimmune inflammation by altering interactions between the transcription factors Foxp3 and RORγt; this reveals an unexpected non-canonical role for Hippo in adaptive immunity.
Autoimmunity can arise when tolerance mechanisms break down. Theofilopoulos and colleagues review how loss of peripheral tolerance, often driven by innate nucleic-acid sensors, leads to the activation of autoreactive lymphocytes that underlie many autoimmune diseases.
Expression of a competent Igh heavy chain initiates a pre-BCR checkpoint during B cell development. Reth and colleagues show that protein arginine methylation by a BTG2-PRMT1 complex is required to inactivate CDK4 and thereby establish pre-B cell arrest.
Vijayanand and colleagues use genome-wide RNA sequencing for transcriptional profiling of CD8+ T cells from tumors and adjacent uninvolved lung tissue from patients with early-stage lung cancer. A tissue-resident memory signature is associated with enhanced cytotoxicity and improved survival.
Monoclonal antibody (mAb) therapy is now commonplace in the clinic, yet such reagents can elicit unwanted side effects due to interactions with Fcγ receptors. Georgiou and colleagues have engineered mAbs that lack such FcγR interactions but retain the ability to activate complement and show that these modified mAbs have efficacious effector function.
Various intracellular pathogens attempt to hide from innate cytosolic sensors by forming vacuoles. Yamamoto and colleagues show that the autophagy-related protein Gate-16, which is induced by interferon-γ, is required for noncanonical autophagy to control infection by Toxoplasma gondii.
Xue and colleagues show that Runx3−/− CD8+ T effector cells aberrantly upregulate genes characteristic of TFH cell lineage and exhibit impaired induction of cytotoxic molecules.
Thymocytes must undergo positive selection to survive and emigrate to the periphery as mature T cells. Glimcher and colleagues identify CHMP5 as a TCR-sensitive regulator of positive selection that acts by preventing oxidation and degradation of the pro-survival protein Bcl-2.
Single-nucleotide polymorphisms in the gene encoding the cytosolic viral sensor IFIH1 are linked to a variety of autoimmune diseases. Rawlings and colleagues demonstrate that one such common polymorphism results in IFIH1 with more-potent activation and can act synergistically with other genetic backgrounds to manifest autoimmune disease.
Genetic polymorphisms affect expression of the atypical chemokine receptor ACKR1 (Duffy) on nucleated erythrocyte precursors. Rot and colleagues show that loss of its expression alters hematopoiesis, yielding a distinct neutrophil population that rapidly exits the bloodstream to give an apparent ‘neutropenia’ phenotype.
TCRβ+CD8αα+ intraepithelial lymphocytes arise from CD4−CD8−CD5+ thymic cells, but the exact precursor source has been not been established. Hogquist and colleagues identify two distinct thymic populations that both give rise mainly to gut-homing intraepithelial lymphocytes.
BACH2 is required for lymphocyte differentiation. Afzali et al. describe mutations that cause BACH2 disruption, immunodeficiency and autoinflammatory disease via haploinsufficiency, a mechanism shared by other super-enhancer-regulated genes.
