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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.
Reboldi and colleagues show that high-cholesterol diets influence IgA secretion. Cholesterol-derived metabolites act on plasma cell GPR183 receptors to alter cell positioning of IgA+ plasma cells within the lamina propria and suppress antibody responses to intestinal pathogens.
Farber and colleagues examine the phenotypic, transcriptomic, clonal, and functional differences between tissue-resident T cells in various barrier tissue sites relative to T cells in lymphoid organs and circulation in humans.
