This study by Wang et al. identifies a role for the T-box transcription factor TBX1 in mediating tissue repair after myocardial infarction. TBX1 is of note clinically as its haploinsufficiency is linked to the cardiovascular and thymic developmental abnormalities seen in DiGeorge syndrome (also known as 22q11.2 deletion syndrome). Using mouse models of myocardial infarction, the authors found that

There have been conflicting views on whether helminth infections modulate disease outcomes during SARS-CoV-2 infection. In this study, Oyesola et al. infected K18-hACE2 mice (which express human ACE2 and are therefore susceptible to SARS-CoV-2) with the lung-migrating helminth Nippostrongylus brasiliensis, waited for the mice to clear the infection, and then infected the mice intranasally with SARS-CoV-2

Interferon-ε (IFNε) is a unique type I IFN that is constitutively expressed by epithelial cells in the female reproductive tract (FRT), where it shows antimicrobial activities. Here, Marks et al. report that IFNε also has anti-tumour functions in the FRT. They found that IFNε is constitutively expressed by epithelial cells in the fallopian tubes of healthy women, but significantly suppressed in low-grade

A new study shows that even a short-term switch to a low-fibre diet suppresses immunity to bacterial infection and compromises effector T cell responses.

Platelet factor 4 reduces inflammation and promotes cognition in the ageing brain.

A study in Nature reports a lactate–HIF1α–NDUFA4L2 pathway in intestinal dendritic cells that regulates the inflammatory priming of encephalitogenic T cells.

Two studies in Nature describe the mechanisms that underlie allergen avoidance behaviour in mice, linking allergen sensing in the gut to a protective behavioural response to repeated ingestion of allergen.

Given the strong pro-inflammatory role of IL-17, agents that target IL-17 or the IL-17 receptor (IL-17R) are attractive candidates for inflammatory diseases. Examples are the IL-17 inhibitor secukinumab and the IL-17R inhibitor brodalumab, which are both approved for the treatment of psoriasis. However, these agents have unexpectedly low efficacy in IL-17-related diseases such as rheumatoid arthritis

Mucosal-associated invariant T (MAIT) cells have an almost invariant TCRα chain that is paired with a restricted repertoire of TCRβ chains and recognize specific microbial metabolites presented by the MHC class I-like molecule MR1. However, some MAIT cells also bind to non-microbial ligands, and alterations in MAIT cells have been observed in non-microbial inflammatory diseases such as diabetes, multiple

Atrial fibrillation (AFib) carries the risk of stroke and heart failure and is the most common arrhythmia. Hulsmans et al. performed single-cell RNA sequencing on atrial tissue from patients with persistent AFib. Compared with healthy control tissues, they found upregulated inflammatory and profibrotic genes and increased numbers of myeloid cells with an inflammatory phenotype. Closer analysis revealed

A preprint by Rakebrandt, Yassini et al. investigates the role of CD4+ T helper cells in heterologous immunity, identifying a population of memory cells that have pro-inflammatory function in a T cell receptor-independent manner.

A study in Immunity reports that a high-fat diet in mice leads to the loss of PPARγ+ Treg cells in the skin, which exacerbates psoriasis mediated by IL-17-producing γδ T cells.

A preprint by Ramanan et al. examines the roles of accessory transcription factors in regulating subsets of colonic regulatory T cells, independently of the microbiota and T cell specificity.

Individuals with the HLA-B*15:01 allele may have pre-existing T cells derived from seasonal coronavirus infections that cross-protect against SARS-CoV-2.

Laboratory mice kept in specific-pathogen free (SPF) conditions are routinely used to dissect the immune system, but they lack the microbial exposures that normally shape the immune system. ‘Rewilding’ systems, which expose mice to environmental microbes while preventing pathogenic infections, are being developed to address this issue and the immune systems of rewilded mice more closely resemble those

Recent studies from the Casanova laboratory and others have shown that autoantibodies against type 1 interferons (IFNs) are linked with negative outcomes to SARS-CoV-2 infection. A new study from Casanova’s group reports that such autoantibodies against IFNs may also explain why some patients develop life-threatening encephalitis following infection with West Nile virus (WNV), despite this virus causing

In mammalian cells, cyclic GMP-AMP synthase (cGAS) senses mislocalized double-stranded DNA (dsDNA) and synthesizes the second messenger cGAMP to activate STING and initiate innate immune signalling. The cGAS–STING signalling pathway originally evolved in bacteria and a cGAS-like receptor (cGLR) that mediates antiviral responses by sensing dsRNA and activating STING was recently described in Drosophila

In contrast to its role in promoting immune responses to viral and bacterial infections, STING inhibits SYK-dependent cytokine production in response to fungal infection.

Bacteria that cause cholera can form unique biofilms on immune cells to promote immune cell death.

A new population of macrophages is identified in mice that expands during lactation and may be important in immune surveillance.

A preprint by Vardam-Kaur et al. reports a role for the ATP transporter PANX1 in regulating effector and memory CD8+ T cells.

A preprint by Nakandakari-Higa et al. introduces universal LIPSTIC (uLIPSTIC), a labelling technique for the detection of physical interactions between any cell types without the requirement for specific receptor–ligand interaction.

In this Tools of the Trade article, Christa Haase (at the Charles Lin lab) describes a technique called Image-seq that enables image-guided cell isolation from a specific, intact tissue location for subsequent single-cell gene expression analysis.

A preprint by Sbierski-Kind et al. shows that IL-33-producing adventitial fibroblasts provide a stromal niche for ILC2s that limits IL-17-mediated liver fibrosis.

Gillian Griffiths and colleagues show that T cell receptor downregulation at the immune synapse occurs through ectocytosis, which terminates receptor signalling and promotes dissociation from target cells.

A combination therapy of a tumour-targeted antibody–cytokine fusion protein and a chemotherapy drug shows promising results in preclinical testing and in a phase I study in patients with recurrent glioblastoma.

Combining inhibition of the histone methyltransferase EZH2 with senescence-inducing drugs can turn immunologically ‘cold’ tumours ‘hot’.

Exploring the signals driving neuroinflammation in multiple sclerosis (MS), Kiss et al. reveal that IL-3 levels are increased in the cerebrospinal fluid of patients with MS relative to controls, and mice lacking Il3 are protected from experimental autoimmune encephalomyelitis, owing to reduced influx of leukocytes into the central nervous system (CNS). CD44hiCD4+ T cells and astrocytes in the CNS were

Bosteels et al. investigated the signals that determine tolerogenic versus immunogenic dendritic cell (DC) maturation. They found that uptake of apoptotic cells induces homeostatic maturation of type 1 conventional DCs (cDC1s, marked by CCR7 expression but low levels of costimulatory molecules). Using CITE-seq, they identified discrete maturation stages, which involved heightened engulfment capacity

Pancreatic ductal adenocarcinoma (PDAC) has very poor survival rates and is largely insensitive to immune checkpoint blockade therapy. Yet, recent studies suggest PDAC harbours more neoantigens than previously thought, with the potential to stimulate T cells. So, Rojas et al. tested whether personalized mRNA vaccines can stimulate neoantigen-specific T cells and provide clinical benefit in PDAC. Their

A preprint by Lad et al. shows that tumour-associated neutrophils in glioblastoma originate from skull bone marrow and acquire an antigen-presenting cell phenotype intratumorally in the presence of local T cells.

Ahn et al. show that bat ASC2 negatively regulates inflammasome activation, which could be exploited to inhibit inflammatory diseases in humans.

Copper(ii) ions promote the metabolic and epigenetic remodelling of macrophages towards a pro-inflammatory state. A copper-binding metformin dimer showed promising results in mouse models of inflammation.

IL-9-producing T helper 9 (TH9) cells are associated with allergic diseases, including asthma, food allergy and atopic dermatitis. The mechanisms regulating these cells are incompletely understood — for instance, it is not clear why TH9 cells gradually lose the capacity to secrete IL-9. Here, Son et al. show that the IL9 locus becomes accessible to STAT5 and STAT6 shortly after TH9 cell differentiation

Nociceptors and dendritic cells (DCs) are prevalent at barrier tissues, including the skin, and imaging studies have suggested these populations interact to shape local tissue immunity. Using in vitro coculture of primary mouse neurons and bone marrow-derived DCs, Hanc et al. found that nociceptors enhance DC production of inflammatory cytokines following exposure to pathogen-associated molecular patterns