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Using a mouse model of ischemic stroke, this study shows stroke-induced lymphangiogenesis at the cribriform plate (CP), suggesting increased drainage of the inflamed brain. Blocking CP lymphangiogenesis with a VEGFR-3 inhibitor improves stroke outcome, but administration of VEGF-C induces larger brain infarcts.

We discovered that PIKFYVE and its product PtdIns(3,5)P2 are essential regulators of Th17 differentiation. Our findings identify molecular mechanisms by which PIKFYVE promotes Th17 differentiation and suggest that PIKFYVE is a potential therapeutic target in Th17-driven autoimmune diseases.

Rapid capture of potentially harmful bacteria in blood by liver macrophages is vital for blood sterility and health. This work reports how naturally occurring antibodies in the plasma enable macrophages to capture and kill blood-borne bacteria in the liver.

IKKα kinase deficiency causes syndromic immunodeficiency and immune dysregulation as a consequence of a major defect in the non-canonical NF-κB pathway as well as a partial defect in the canonical NF-κB pathway.

Cigarette smoke is a diverse mix of chemicals that bind the antigen-presenting protein MR1 and modulate MAIT cell function in the lung through diverse mechanisms, impacting their ability to respond to respiratory infections and potentially contributing to disease.

This study identifies 11 IFNAR1 alleles impairing IFN-α/ω responses but sparing IFN-β, including an allele common in Southern China (P335del). Heterozygous variants show dominant negative effects, linking these variants to increased susceptibility to respiratory and cerebral viral diseases.

Technical Advances and Resources

This work shows that hepatoblasts in the fetal liver are the primary source of factors that sustain blood cell production. Different hematopoietic progenitors exhibit distinct preferences for neighboring stromal cells and show developmental changes in spatial distribution.

Brief Definitive Report

α-Galactosylceramide (α-GalCer), a marine sponge-derived canonical antigen for invariant natural killer T (iNKT) cells, has not been detected in mammals. In this study, we report the molecular detection of α-GalCer in mammals using supercritical fluid chromatography tandem mass spectrometry.

Differentiation of tissue-resident memory T cells (TRM) is accompanied by the upregulation of the conventional DC1 (cDC1) chemoattractant, Xcl1. Modulation of the XCL1–XCR1 chemokine axis influences intestinal tissue residency and antitumor immunity.

This study investigates how different lymphatic drainage pathways from the central nervous system regulate cerebrospinal fluid homeostasis, highlights the role of lymphatic pathways in maintaining CSF dynamics, and suggests therapeutic potential in modulating these pathways in CNS disorders.

Insights

In this issue, Hosono and co-workers characterize a putative self-glycolipid that engages the iNKT cell TCR when bound to CD1d. The expression and distribution of this compound help to explain some of the unusual properties of invariant NKT cells.

People & Ideas

Professor Cindy Ma heads the Human Immune Disorders Laboratory at the Garvan Institute of Medical Research. She is a member of the Garvan Faculty, holds a conjoint appointment with UNSW Sydney (School of Clinical Medicine, Faculty of Medicine and Health), and is an NHMRC of Australia Investigator Grant Fellow (L1).

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