Volume 20 Issue 10, October 2019

A new study has identified various previously unknown mutations in the genes encoding human and mouse A20 that affect its phosphorylation and its function as an inhibitor of the transcription factor NF-κB, with implications for immunity and inflammatory disease.

Transcription-factor paralogs are not equivalent and serve distinct roles in immune cells. Analysis of the RUNX family of transcription factors reveals insights into the non-redundant roles of RUNX1 and RUNX3.

Cellular metabolic screening identifies hyper-respiration, induced by gain-of-function mutations in the gene encoding succinate dehydrogenase, as a disease-driving immunometabolic trait of B cells from patients with primary antibody deficiency.

A specifically engineered Zika subunit vaccine based on the viral envelope protein mediates protective immunity in mice without inducing the cross-reactive antibodies responsible for antibody-dependent enhancement of infection with dengue virus.

Zhu and colleagues discuss the forces that affect the ligand recognition, receptor triggering and signal transduction downstream of immunoreceptors, and their implication on lineage decision and effector function.

Marsland and colleagues review the role of the lung and gut microbiotas in respiratory health and disease.

Screaton and colleagues describe a protective Zika virus E-dimer-based subunit vaccine engineered to abrogate antibody-dependent enhancement of dengue infection.

A20, encoded by TNFAIP3, is a negative-feedback inhibitor of NF-κB. Grey and colleagues identify natural human variants of TNFAIP3, which lower A20 activity and increase autoinflammatory responses. These alleles were inherited by descendants of Denisovans who crossed the Wallace Line to inhabit Oceania.

Hess and colleagues perform metabolic screens in B cells from patients with primary antibody deficiency and find that germline mutations in the succinate dehydrogenase subunit SDHA drive the expression of the cytokine IL-6 in patients with persistent polyclonal B cell lymphocytosis.

Beutler and colleagues identify skywarp (swp) mice, which exhibit a hypomorphic variant of the U5 splicing protein SNRNP40 and aberrant mRNA splicing specifically in lymphocytes and hematopoietic stem and progenitor cells, suggesting alternative splicing influencing immune cell function.

Exhaustion is an acquired state of T cell dysfunction. Sharpe and colleagues demonstrate that the phosphatase PTPN2 supports a T cell-intrinsic exhaustion program in both chronic infection and cancer models.

PlGF is an important vascular endothelial growth factor which has not been widely implicated in immune function. Kim and colleagues demonstrate that PlGF is selectively secreted by T_H17 cells to promote angiogenesis but in turn also strongly supports T_H17 cell differentiation yet inhibits regulatory T cell function.

The precise role of follicular regulatory (T_FR) cells in the control of the germinal center (GC) reaction is unclear. Sage and colleagues develop a T_FR cell-deleter mouse that allows specific temporal deletion and show that T_FR cells primarily control early but not late GC responses.

Protein transcription factor paralogs are not equivalent and serve distinct roles in immune cells. Merkenschlager and colleagues show that RUNX1 and RUNX3 differ in binding strength to motif sequences and how this leads to differential functional activities.

Love and colleagues show that β-selection-associated proliferation requires the combined activity of SCF ubiquitin ligases that contain the F-box proteins Fbxl1 and Fbxl12, which are induced by Notch and pre-TCR signals, respectively.

Pre-B cells undergo a transition checkpoint needed for developmental progression. Mandal and colleagues show that the CXCL12–CXCR4 signaling axis orchestrates late B cell lymphopoiesis by suppressing Myc and cyclin D genes and promoting Rag-mediated recombination of immunoglobulin light-chain genes.