Volume 20 Issue 7, July 2019

On 18 December 2018, the National Institute of Allergy and Infectious Diseases convened a workshop entitled ‘Recent Advances and Opportunities in the Development and Use of Humanized Immune System Mouse Models’.

Novel single-cell profiling technologies have delineated the cellular and molecular landscapes that dominate the joints in rheumatoid arthritis and the skin and kidneys in systemic lupus erythematosus, shedding light on potential pathogenic mechanisms.

Although the molecular basis of most disease-associated single-nucleotide polymorphisms has remained elusive, an HIV-1 viral load–associated polymorphism (rs1015164) has been identified that marks expression of a long non-coding RNA that regulates the co-receptor CCR5 and thereby influences infection of CD4⁺ T cells.

The cytokine IL-15 controls the homeostasis and activation of CD8⁺ T cells and natural killer cells. A new study reveals the deubiquitinase Otub1 to be a negative regulator of IL-15 signaling, with important consequences for autoimmunity and anti-cancer immunity.

In this Review, Natoli and Ostuni discuss the mechanisms of adaptation and memory in immunity, with the aim of providing basic concepts that rationalize the properties and molecular bases of these essential processes.

In this Review, Pearce and colleagues discuss the metabolic adaptation of immune cells to various tissues and how functional adaptation compared with maladaptation within the niche can affect tissue homeostasis.

In this Review, Chavakis and colleagues discuss the mechanisms that govern the adaptation of hematopoietic progenitor cells to inflammation and its effects on the pathogenesis of human disease.

RIG-I is an RNA sensor and is required for effective antiviral immunity. Cao and colleagues demonstrate that the previously undescribed long noncoding RNA Lnczc3h7a serves an essential scaffolding role in supporting productive RIG-I signaling.

Multiple genetic variants have been identified that influence the outcome of HIV infection. Carrington and colleagues investigate the mechanism of one of the strongest variants, rs1015164, and show that it influences expression of a lncRNA controlling CCR5 expression.

Many tumors evade immunosurveillance by down-modulating expression of antigen-processing machinery and MHC molecules. Yang et al. report triple-negative tumor cell expression of the lncRNA LINK-A enhances degradation of antigen peptide-loading complex molecules and intrinsic tumor suppressors, which contribute to tumor persistence.

Ginhoux and colleagues show that the priming of mouse hematopoietic progenitor cells toward the pDC lineage occurs at the common lymphoid progenitor stage.

Natural killer cells have important roles in virus and anti-cancer responses. Glimcher and colleagues demonstrate that a natural killer cell-intrinsic endoplasmic reticulum stress pathway is essential for their proper function.

IL-15 has important functions in the activation and homeostasis of cytotoxic T lymphocytes (CTLs) and NK cells. Sun and colleagues demonstrate that the deubiquitinase Otub1 controls CTLs and NK cells in a cell-intrinsic manner by negatively regulating IL-15 signaling.

Long-lived, self-renewing ‘progenitor-like’ CD8⁺ T cells can arise during chronic viral infection or in cancer. Wu and colleagues identify the transcription factor TOX as essential to endow ‘stemness’ and long-term persistence in the face of chronic infection.

Much about the kidney-resident immune populations is a black box. Hacohen and colleagues use single cell RNA sequencing of kidney, skin and urine from lupus nephritis patients to describe the transcriptional state of the immune cells present in each compartment.

Nephritis is a major cause of lupus morbidity. Putterman and colleagues use single-cell RNA sequencing on human renal and skin biopsies to describe the expression landscape associated with lupus nephritis.

Defining cell types and their activation status in rheumatoid arthritis (RA) is critical to understanding this disease. Raychaudhuri and colleagues leverage several single-cell -omics approaches to define the cellular processes and pathways in the human RA joint.