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Brain cells that die after stroke release intracellular proteins into their environment. Akihiko Yoshimura and his colleagues demonstrate that peroxiredoxin proteins released from dying cells induce inflammatory cytokine expression and drive brain damage after stroke.

Inflammatory cells invade the brain after stroke, but their role in disease has been unclear. Now, Akihiko Yoshimura and colleagues report that a particular population of T cells that express the inflammatory cytokine IL-17 plays a key role in stroke progression: depletion of these cells—even as late as 1 day after stroke—can alleviate brain injury in mice pages 844–846).

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

Clonally expanded CD8 +T cells drive early Alzheimer’s pathology by suppressing microglial amyloid clearance through CCL5-CCR5 signaling, but later adopt protective roles, thereby revealing a stage-dependent functional transition.

Transfer of NR4A-deficient T cells expressing chimeric antigen receptors is shown to reduce tumour burden and increase survival by shifting T cell transcriptional programs away from exhaustion and towards increased effector function.

In this Review, Akihiko Yoshimura and collegues discuss the most recent advances in our understanding of suppressor of cytokine signalling (SOCS) proteins in the regulation of immunity, their involvement in human diseases and the therapeutic implications of targeting this family of cytokine regulators.

Klebsiella pneumoniae from the gut microbiota of patients with primary sclerosing cholangitis (PSC) can damage the intestinal epithelial barrier, resulting in bacterial translocation and T helper 17 cell responses in the liver, indicating a role in PSC pathogenesis.

Members of the SOCS (suppressor of cytokine signaling) family negatively regulate STAT transcription factors. The SOCS family member CIS is now shown to negatively regulate differentiation into the T_H2 and T_H9 subsets of helper T cells through negative regulation of STAT3, STAT5 and STAT6.

The gut is populated by a myriad of microorganisms and how the immune system tolerates their presence is of great interest. Here, by studying colon morphology in multiple knockout mice, the authors demonstrate a potential role for prostaglandin E2 and SOCS1 in mediating immune tolerance.

The structure of the Golgi and the localization of glycosylation enzymes remain largely elusive. Here, the authors use super-resolution microscopy to show that the Golgi is composed of small dynamic units which have rapidly moving zones of glycosylation enzymes.

The substitution of oxygen by hydride anions in oxide materials to form oxyhydrides has been difficult to achieve because it requires highly reducing conditions without transferring an electron from the hydride. An oxyhydride of BaTiO₃ that is electronically conducting, stable in air and water at ambient conditions, and exchangeable with hydrogen gas at 400 °C, has now been prepared.

Regulatory T cells are characterized by the expression of Foxp3, however, how the expression of this protein is controlled is unclear. Here, the authors show that the nuclear orphan receptor, Nr4a2, is a transcriptional activator of Foxp3, and suggest that it is required for the function of regulatory T cells.

Tumour-specific T cells can be expandedin vitroand adoptively transferred for therapy, but this strategy is limited by induction of short-lived T cell populations. Here the authors activate Notch signalling in cultured mouse or human T cells, resulting in the production of a long-lived stem cell memory T cell population that can fight tumours in mice.

Activation of inflammasome contributes to several pathologies. Here, the authors show that Bruton’s tyrosine kinase is essential for NLRP3 inflammasome activation, and that blocking it with the FDA-approved inhibitor ibrutinib limits tissue damage in a mouse model of ischaemic stroke.

Sekiya and colleagues demonstrate that the Nr4a nuclear receptors, which are encoded by immediate-early genes upregulated by TCR stimulation in thymocytes, have an essential role in regulatory T cell development.

The reasons why influenza infection promotes a broader antibody response compared with vaccines are not fully understood. Here the authors show that unmasking of haemagglutinin epitopes and IL-4 signals in the germinal centre contribute to broader antibody responses after infection.

The synthesis of NPY and its receptor Y1R increases in lung phagocytes during severe influenza virus infection, leading to the induction of SOCS3 and impaired antiviral response and increased pro-inflammatory cytokine production.

Cancer cells develop resistance to tyrosine kinase inhibitors targeting EGFR. Here, the authors explore the mechanism of resistance to one such inhibitor - osimertinib - and find that resistance is caused by increased expression and activation of the IGF1 receptor and subsequent activation of the donwstream signalling pathway.

PD-L1 expression by senescent cells renders them resistant to clearance by CD8 T cells, suggesting PD-L1 as a target for mitigating the effects of ageing.

The scavenger receptor MSR1 contributes to the clearance of damage-associated molecular patterns (DAMPs) by infiltrating myeloid cells in the post-stroke rodent brain. Myeloid cell MSR1 deficiency impairs clearance and exacerbates stroke-induced impairments, whereas a pharmacological intervention to boost MSR1 expression improves pathological and functional outcomes.

Whole-genome sequencing identifies noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and oculopharyngeal myopathy with leukoencephalopathy, three disorders with overlapping clinical features and neuroimaging findings.

A liver–brain–gut neural circuit responds to the gut microenvironment and regulates the activity of peripheral regulatory T cells in the colon by controlling intestinal antigen-presenting cells in a muscarinic signalling-dependent manner.

This study demonstrates the activation of a STAT3-independent healing pathway in response to mucosal injury which involves the co-receptor for IL-6 cytokines gp130 and downstream effectors Src, Yes, YAP and Notch.

In two studies from teams led by Hiroshi Kawaguchi and Jang-Soo Chun, a role for HIF-2α in osteoarthritis has been uncovered. Along with identifying the molecular mechanism, the teams found that HIF-2α expression is increased in human osteoarthritic tissue, and mice deficient for the protein are protected in two osteoarthritis models, suggesting that HIF-2α could be a therapeutic target.

Inactivating the CLP1 RNA kinase in mice leads to a progressive loss of motor neurons, through a mechanism related to the accumulation of a novel set of small RNA fragments derived from aberrant processing of tyrosine pre-transfer RNA.

Little information is available on molecular changes in response to treatment of rheumatoid arthritis (RA). Here the authors report a multi-omics study collecting patients' transcriptome, proteome, and immunophenotype data to help understand the impact of drug treatments on RA molecular phenotypes.

In a mouse model of ischaemic stroke, regulatory T cells infiltrate the injured brain in response to the chemokines CCL1 and CCL20 and suppress excessive astrogliosis via the production of amphiregulin.