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Marichal and colleagues use a model of niche depletion and refilling to show that engrafted Ly6C+ classical monocytes proliferate locally in a Csf1 receptor-dependent manner before differentiating into lung interstitial macrophages.
Cheng et al. demonstrate that an extra copy of the X-linked epigenetic regulator UTX in females increases natural killer (NK) cell effector function. As NK cells are critical for antiviral immunity, this may explain decreased severity of viral infections in females compared to males.
Dalod and colleagues utilize a combinatorial genetic reporter strategy to uniquely mark plasmacytoid dendritic cells (pDCs) in mice. They utilize these mice to identify bona fide pDCs and functionally characterize before and during viral infection, in comparison to several other DC types.
Lo and colleagues provide evidence for the TCR kinetic proofreading model by LAT Gly135Asp alteration to reveal functional consequences of altered kinetics in TCR activation in thymic selection and mature T-cell responses.
Zhang and colleagues perform functional, biochemical and structural analysis of a set of antibodies isolated from COVID-19 convalescents infected with wild-type SARS-CoV-2 during the first wave of the pandemic and show they have broad neutralizing activity against all SARS-CoV-2 variants tested, including omicron.
Robbiani and colleagues show that antibodies against specific chemokines are detected in COVID-19 convalescents and may modulate the inflammatory response and disease outcome.
Here, the authors show that CD8+ T cells egress from tumors via lymphatic vessels in a CXCL12/CXCR4-dependent manner. High-affinity antigen encounter inhibits CXCR4 and increases retention, while no encounter or weak affinity directs T cell exit to limit local tumor control.
Unlike metabolic reprogramming that is characteristic of macrophage inflammatory polarization responses to lipopolysaccharide and TLR4 stimulation, the metabolism underlying inflammatory responses to CD40 signaling is not well characterized. Here the authors show CD40 signaling drives fatty acid oxidation and glutamine metabolism resulting in regulation of the NAD+/NADH ratio, which in turn promotes antitumor and pro-inflammatory macrophage functions.
Type 1 diabetes is associated with homozygous expression of specific major histocompatibility complex class II beta chain polymorphisms. Here the authors show that the disease-protective effect of major histocompatibility complex class II heterozygosity is conferred by non-cognate thymocyte negative selection.
Benhar and colleagues provide an atlas of non-neuronal cells in the adult mouse retina at steady state and after optic nerve injury and identify key cellular and molecular events along the path of neuronal degeneration after injury.
Here, the authors show that acute influenza infection induces trained immunity in self-sustaining resident alveolar macrophages, which independently exert long-term antimetastatic immune surveillance in the lung via enhanced tumor killing.
Here the authors show that dihydroorotate dehydrogenase in the de novo pyrimidine synthesis pathway functions as a cell fate checkpoint that can be targeted to specifically diminish the number and function of effector T cells without affecting the memory T cell pool and response to infection.
Savage and colleagues identify a population of CD4+ T cells within the endogenous repertoire that exhibit hallmarks of overt self-reactivity, spontaneously adopt a follicular helper T cell phenotype and are enriched in non-lymphoid organs following sustained Treg cell depletion.
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.
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.