Proal and colleagues review the evidence for long-term persistence of coronavirus SARS-CoV-2 in tissues of infected individuals and discuss how this viral reservoir may contribute to the pathogenesis of post-acute sequelae of COVID-19 (PASC).

Chi and colleagues identify brain-resident CXCR6⁺PD-1⁺CD8⁺ T cells that interact with resident microglia to limit immune-mediated pathology in a mouse model of Alzheimer’s disease.

Verdeil and colleagues show that the transcription factor NFAT5 is selectively required in tumor-induced, but not chronic infection-induced, CD8⁺ T cell exhaustion, possibly due to the modulation of NFAT5 activation by hyperosmolarity in the tumor environment.

Iron metabolism has been shown to play an important role in the development and function of the immune system, but its role in ILC3s is unclear. Here the authors show that CD71-mediated iron metabolism controls ILC3 proliferation and the host response to Citrobacter rodentium infection and CD71 expression is regulated by Ahr signaling.

Satija and colleagues use multimodal sequencing technologies and cross-modality integration tools to define distinct subpopulations of CD8⁺ T cells that are predictive of COVID-19 severity.

Wherry and colleagues define the kinetics of vaccine-primed recall immune responses during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection, highlighting rapid activation of memory T cells and broadly enhanced immune responses in previously vaccinated individuals.

The mechanisms by which noncoding genetic variation shapes tissue macrophage phenotypic diversity remain obscure. Glass and colleagues define cell-intrinsic and environmental effects contributing to genetic control of Kupffer cell transcription.

Verdeil and colleagues show that the transcription factor NFAT5 is selectively required in tumor-induced, but not chronic infection-induced, CD8⁺ T cell exhaustion, possibly due to the modulation of NFAT5 activation by hyperosmolarity in the tumor environment.

Iron metabolism has been shown to play an important role in the development and function of the immune system, but its role in ILC3s is unclear. Here the authors show that CD71-mediated iron metabolism controls ILC3 proliferation and the host response to Citrobacter rodentium infection and CD71 expression is regulated by Ahr signaling.

Santosa et al. show that IRF4 is upregulated upon NK cell activation and acts as a signal integrator for the differentiation and expansion of mouse cytomegalovirus-specific NK cells by partly controlling nutrient uptake required for adaptive NK cell responses.