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Group 2 Innate lymphoid cells (ILC2) are a source of type 2 cytokines, such as interleukin-5 (IL-5). Here Troch, Jakob et al. show a non-redundant role of ILC2-derived IL-5 required for the development and function of a subset of murine B cells.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Specific deletion of group 2 innate lymphoid cells in mice shows these cells have roles in the recruitment of eosinophils and in mounting immune and epithelial type 2 responses.

A γδ T cell–IL-3 signalling axis is defined that controls the allergen responsiveness of cutaneous sensory neurons, leading to evidence for an immune rheostat that governs sensory neuronal responses to allergens on first exposure.

A large international panel of experts reach consensus on a new standard for reporting settings in psychedelic trials, identifying 30 key non-pharmacological factors to strengthen the rigor of psychedelic research.

A microfluidics approach that links short sequence reads enables haplotype construction and complex variation identification from tiny amounts of input DNA.

Ronchese and colleagues show that IL-13 secreted homeostatically by dermal ILCs contributes to the differentiation of a CD11b^lo type 2 dendritic cell subset, which supports the development of T_H2 cells and curtails the development of T_H17 cells in the skin of mice and humans.

Alterations in commensal bacteria are associated with an increased risk of allergic disease. David Artis and his colleagues now report that commensal-derived signals influence basophil development and T_H2 cytokine–dependent allergic airway inflammation by suppressing serum IgE levels. Individuals with hyper IgE syndrome also have elevated circulating basophil numbers, suggesting a mechanistic link between commensal bacteria, B cell–mediated production of IgE and basophil hematopoiesis.

Asthma is caused by hyperreactivity to benign antigens, with humoral immunity orchestrated by interleukin-4 (IL-4) and IL-13 being the key etiological factor. Here the authors show, in humanized mouse models, that dual vaccination against IL-4 and IL-13 induces their durable suppression ameliorate experimental asthma, and to hint clinical translation.

A hyper-stable de novo protein mimic of interleukin-2 computationally designed to not interact with a regulatory T-cell specific receptor subunit has improved therapeutic activity in mouse models of melanoma and colon cancer.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Here, the authors characterize immunological and microbiome alterations in a cohort of obese asthmatics, finding that disease severity negatively correlates with fecal abundance of Akkermansia muciniphila, and show in a mouse model that administration of A. muciniphila reduces airway hyper-reactivity and airway inflammation.

Dietary inulin fibre alters the composition and metabolism of gut microbiota, resulting in elevated levels of bile acids that subsequently trigger mucosal type 2 inflammation characterized by eosinophilia, with clinical implications for allergy and anti-helminth defence.

In this study, the authors report that post-vaccination neutralizing and binding antibody levels in the ENSEMBLE trial associate with Ad26.COV2.S vaccine efficacy (VE) against severe-critical COVID-19, with substantial VE even at unquantifiable neutralizing antibody titer.

Neurological prognostication in patients who remain in hypoxic–ischaemic coma after cardiac arrest has always been challenging, and has become even more so since the advent of therapeutic hypothermia (TH). In this Review, Greer et al. consider how neurological outcomes and prognostic indicators might be influenced by the use of TH, and discuss advances in neuroimaging and electrophysiology that are expected to aid neuroprognostication in this patient population.

The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive loci conferring either risk or protection to schizophrenia.

Studies of humans, mice and nematodes reveal a conserved role of neural activity and the transcription factor REST in extended longevity.

IL-33, released by epithelial cells in response to stress, is a potent activator of inflammation. Here Cohenet al. show that secreted IL-33 is rapidly inactivated by disulfide bond formation that prevents binding to its receptor, and that IL-33-related cytokines are susceptible to similar oxidation.

This study uses single-cell sequencing to investigate the diversification of cortical cell types during evolution. Comparisons across brain regions and species identify molecular signatures of ancestral cell types in the mammalian olfactory cortex.

Chronic inflammation of the airways is associated with remodeling and fibrosis, leading to a progressive decline in lung function in people with severe asthma. Michael Croft and his colleagues report that in mouse models of allergic lung inflammation expression of the TNF family member LIGHT is induced. Blockade of LIGHT prevents remodeling, providing a therapeutic strategy to prevent asthmatic airway remodeling.

SARS-CoV-2 variants with mutations in spike have emerged during the pandemic. Magaret et al. show that in Latin America, efficacy of the Ad26.COV2.S vaccine against moderate to severe–critical COVID-19 varied by sequence features, antibody escape scores, and neutralization impacting features of the SARS-CoV-2 variant.

Neuromedin receptor NMUR1 is specifically expressed by a subpopulation of type 2 innate lymphoid cells and promotes the inflammatory response of these cells in response to allergens, indicating the importance of neuro-immune crosstalk in allergic responses.

Increased salt concentrations are shown to induce murine and human T_H17 cells by a mechanism that depends on activation of p38/MAPK, NFAT5 and SGK1; mice kept on a high-salt diet develop a more severe experimental autoimmune encephalomyelitis due to increased induction of T_H17 cells.

Type 2 responses can be elicited by ILC2s and T_H2 cells. Locksley and colleagues show that the epithelium-derived cytokines IL-25, IL-33 and TSLP are required for full effector activation of poised ILC2 and primed T_H2 cell populations.

Unlike ferrocene and its cationic counterpart ferrocenium, the ferrocene monoanion is an unusual species that has been observed through low-temperature electrochemical studies. Now, a family of isostructural 3d metallocenates has been isolated that consists of a manganocene, a cobaltocene and a high-spin ferrocene anion stabilized by cyclopentadienyl ligands bearing bulky aliphatic groups.

Alzheimer’s disease is associated with changes in astrocytes. Here the authors investigated the astrocyte translatome associated with amyloid-ß and tau pathology.

Gold-standard evidence for correlates of protection is provided by analysis of a randomized phase 3 trial of Ad26.COV2.S for protection against moderate to severe-critical COVID-19 disease.

It is debated how follicular helper T (Tfh) cells versus central memory CD4⁺ T cells arise from similar precursors, and little is known about the regulation of germinal-centre (GC)-Tfh cell differentiation. Here, authors establish markers in the early precursor stage that distinguish between the GC-Tfh and memory T cell fates and identify an important mechanism that regulates the competitive fitness of the GC-Tfh cells.

Physiologically relevant stimulation of dopamine neurons does not function as a reward and does not endow cues with a reward representation. However, high-frequency stimulation is represented as a sensory-specific goal that motivates behavior.