Volume 18 Issue 7, July 2017

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.

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.

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.

Davis and colleagues review systems-biology approaches in immunology as a powerful means of understanding the immune system as a whole.

Intracellular detection of viral invasion triggers activation of the transcription factor IRF3 and antiviral interferon production. Fangfang Zhou and colleagues report that the transcription regulator YAP in the host restrains this process by preventing inadvertent spontaneous dimerization of IRF3 and its translocation to the nucleus.

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.

Jackson and colleagues show that dendritic cells transit to the lumen of lymphatic vessels through hyaluronan-mediated interactions with the endothelial receptor LYVE-1.

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.

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.

Wucherpfennig and colleagues show that the microRNA miR-31 increases the sensitivity of T cells to type I interferons, which interferes with effector T cell function during chronic infection.

Hippo signaling controls cell and tissue growth. Geng et al. show that Hippo signaling is required for T_H17 cell differentiation but inhibits T_reg cell differentiation.

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.