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Intrathymic dendritic cell (DC)-biased precursors act as hematopoietic stromal cells that support the generation of human T cell progenitors from hematopoietic progenitor cells, via crosstalk with immature thymocytes that express TNF receptor 2. This function of DC precursors can be exploited to generate T cell precursors and competent T cells for cell therapy.
Here, the authors show that IFNγ binding to heparan sulfate is a mechanism to restrain IFNγ at the site of production, thereby preventing high systemic levels of this cytokine and associated immunopathology.
Here the authors show how metabolic alteration of acyl chain composition affects phosphoinositide-driven signaling to initiate and sustain CD8+ T cell effector function during cell differentiation.
In addition to the acute phase of SARS-CoV-2 infection, a significant percentage of patients experience a prolonged illness with varying symptomatology. Longitudinal SARS-CoV-2 patient-centric immunologic, inflammatory and metabolic data collection has allowed the generation of a composite signature to predict recovery.
Ruffieux, Hess and colleagues analyze longitudinal phenotyping of patients with coronavirus disease 2019 to show that covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites influence the restoration of homeostasis, the risk of death and that of long COVID.
Murre and colleagues identify a specific enhancer, E34, within the Igk locus that is required for chromatin remodeling and repositioning to promote Rag-mediated Igkv7-33 Vκ-Jκ gene recombination, needed for generation of anti-phosphorylcholine-specific antibodies. Mice lacking E34 are more susceptible to Streptococcus pneumoniae infections.
In humans, intrathymic development of DCs is evident but its physiological significance is unknown. Taghon et al. show intrathymic development of DCs as hematopoietic stromal support for the early stages of human T cell development via IRF8-driven transmembrane TNF.
Tanaka and colleagues show that an SNX25–Nrf2 pathway in dermal macrophages sets the threshold for pain sensitivity through modulating the production of the neurotrophic factor NGF.
TH17 cells combat infection but can also drive pathological inflammation. A TH17 cell NLRP3–caspase-8–caspase-3–GSDME axis is now shown to release the alarmin IL-1α without triggering cell death.
Human resident memory T (TRM) cells clonally segregate in distinct tissues, with gene expression signatures tailored to those sites. Hence, beyond a shared language of residency, TRM cells may acquire local dialects to provide site-specific immunity.
Caligiuri and colleagues show that the m6A reader YTHDF2 modulates the inflammatory activation and antitumor function of tumor-associated macrophages in part by modulating the stability of Stat1 mRNA.
Colonna and colleagues report dysregulated gene expression in microglia harboring homozygous mutations of DAP12 from individuals with Nasu–Hakola disease, a form of early-onset dementia.
