Volume 21 Issue 7, July 2020

Frank Carbone describes how his lab identified a new class of memory T cells that permanently reside in the tissues.

Nature Immunology’s 20^th anniversary is a good opportunity to reminisce about the ImmGen collective endeavor — its goals, successes and horror stories — and the group’s exploration of various modes of scientific publishing.

Paola Ricciardi-Castagnoli describes how her groups’ focus on mucosal immunity led to the discovery of how dendritic cells sense the gut microbiota to maintain homeostasis.

Takashi Fujita’s discovery of RNA helicases as intracellular viral replication sensors illustrates how scientific knowledge develops in logical — and sometimes illogical — ways.

Fred Ramsdell and Alexander Rudensky revisit the discovery of the Foxp3 gene and its foundational role in the differentiation and function of regulatory T cells.

Katerina Akassoglou recounts how her work on the mechanisms and functions of blood leaks in the brain led to the discovery of fibrin-targeting immunotherapy.

Immunologists used to avoid metabolism, but that is no longer possible. Now that we must talk about it, how can we do so in a way that enhances and clarifies our understanding of the role metabolism plays in the immune response?

Host cell cholesterol is often exploited by pathogens for entry and egress. Two new studies elucidate a new interferon-inducible mechanism by which cells limit plasma membrane cholesterol to promote antibacterial defense.

Caspase-cleaved gasdermin D forms pores in cellular membranes, thus executing proinflammatory cell death by pyroptosis. Disulfiram — a drug used to treat chronic alcoholism — is now found to be an inhibitor of pore formation, which may therapeutically counteract exacerbated inflammation in sepsis and beyond.

CXCR3⁺ regulatory T cells, known to limit type 1 immune responses, can promote tissue-resident immunity by providing bioactive transforming growth factor-β to CD8⁺ T cells.

Early plasmablasts responding to Plasmodium infection may outcompete germinal center B cells for l-glutamine and delay pathogen control.

The identification of the acute phase protein serum amyloid A as a soluble allergen sensor sheds new light on the mechanisms involved in the induction of type II airway inflammation.

Zhao and colleagues show that STING activation is sensitive to membrane lipid peroxidation that occurs upon reactive oxygen species (ROS) production. The lipid hydroperoxidase glutathione peroxidase 4 (GPX4) reduces such oxidized lipids. Lack of GPX4 leads to STING protein carbonylation, which impedes its trafficking from the ER to the Golgi.

Disulfiram is an FDA-approved drug for treating alcoholism. Wu and colleagues show that disulfiram can be repurposed to efficiently inhibit pyroptosis by specifically blocking gasdermin-mediated pore formation.

Bensinger and colleagues show that interferons promote host cell resistance to bacterial cytolysins by decreasing cholesterol synthesis and promoting the esterification of cholesterol, which alters the availability of this pool of ‘free’ cholesterol needed for pore formation.

Smole and colleagues show that the soluble pattern recognition receptor serum amyloid A (SAA) recognizes several mite allergenic proteins, including Der p 13 and Blo t 13, which are conserved fatty acid-binding proteins. Such FABP–SAA1 binding triggers epithelial cell release of the type-2-promoting cytokine IL-33, which in turn drives IL-13 production and allergic syptoms.

Tissue-resident memory T (T_RM) cells provide rapid front-line protection against infection. Veldhoen and colleagues demonstrate that the type 1 regulatory T cell subset supports generation of T_RM cells.

Bcl-6 is the signature transcription factor for T_FH cells. Crotty and colleagues provide a comprehensive transcriptional map depicting the regulatory circuitry controlled by Bcl-6 in determining T_FH cell fate and function.

Early humoral responses to malaria fail to induce durable protective antibodies. Butler and colleagues report that low-affinity, short-lived plasmablasts become nutrient sinks for glutamine and starve germinal center B and T cells, thereby reducing the generation of high-affinity B cells and long-lived plasma cells and memory B cells.

Microglia have key roles in central nervous system (CNS) disease and homeostasis but their study can be challenging. Prinz and colleagues identify hexosaminidase subunit beta (Hexb) to be specifically expressed by microglia and stable even under inflammatory conditions.