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Brief Definitive Report

The study identifies a unique role for early T-bet expression in promoting the proliferation of antigen-specific CD8+ T cells following vaccination. Early T-bet expression is necessary for optimal LFA1 expression for appropriate cellular interactions and enables optimal expansion and differentiation of effector and memory CD8+ T cells.

Nielsen and Zhang et al. show that well-established, Notch4-induced brain arteriovenous malformations are normalized, following deletion of the Notch signaling mediator, Rbpj. Upon complete regression, virtually no AVM relapses in adults, even when the causal factor is reintroduced.

Arachnoid granulations are poorly investigated. We show that they harbor immune cells and communicate with perisinus spaces, suggesting that granulations subserve neuroimmune roles and function as transarachnoidal passageways. These data raise new theories regarding glymphatic–lymphatic coupling and mechanisms of diseases.

We report a new mechanism of immune evasion by SARS-CoV-2 based on direct disabling CTLs to form immune synapses through Spike protein binding to ACE2. This mechanism could contribute to the failure of the immune system to control SARS-CoV-2 infection.


Using systemic EC–pericyte crosstalk analysis, this study identifies the NO–sGC as a key signaling that mediates EC–pericyte communication in the lung vasculature and demonstrates that pharmacological activation of the NO–sGC signaling promotes vascular integrity and mitigates inflammation-induced lung injury.

Coffelt, Edwards, and colleagues provide deep phenotypic analysis of mouse γδ T cells. They focus functional studies on IL-17A–producing γδ T cell subsets, showing that the co-inhibitory molecules, PD-1 and TIM-3, regulate cell expansion in tumor-bearing mice, which counteracts anti–PD-1 or anti–TIM-3 immunotherapy.

How an anomaly in a TCR signaling molecule leads to spontaneous autoimmunity over immunodeficiency is unclear. Qualitative/quantitative reduction of ZAP-70 to a critical range produces autoimmune T cells and impairs Treg function, together eliciting autoimmune arthritis and colitis in mice.

Zhou et al. establish murine models of anti-CTLA-4–mediated intestinal irAEs. These reveal common immune signatures and the importance of fecal microbiome dysbiosis as irAE-driving mechanisms, which enable preclinical therapeutic interventions. Key immune features are validated in a cohort of melanoma patients with ICB-associated intestinal irAEs.


Postmortem microstructural studies together with in vivo magnetic resonance imaging show that human arachnoid granulations are porous channels that serve as transient filtration conduits for cerebrospinal fluid to flow directly into dural interstitial tissue, but not into venous sinuses.

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