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Sieweke and colleagues show that alveolar macrophages maintain a core gene expression program even after several months in culture, and reacquire full transcriptional and epigenetic identity after transplantation into the lung.
The binding of PD-L1 to CD80 on antigen-presenting cells prevents PD-1 ligation on T cells. Therapeutic blockade of the cis-PD-L1–CD80 interaction liberates PD-L1 to bind to PD-1, inhibits autoreactive T cells and robustly alleviates autoimmune symptoms.
Increasingly, human monoclonal antibodies have been deployed against COVID-19, but combinations are typically needed for recognition of diverse viral variants. Bispecific antibodies could make the task of manufacturing and delivering combinations more efficient.
Crosstalk between the dendritic epidermal γδ T cell (DETC) T cell receptor and Skint1 expressed by keratinocytes at steady state regulates epidermal barrier function and maintains DETC responsiveness.
A delayed second dose relative to the standard 3-week schedule for the BNT162b2 mRNA vaccine against SARS-CoV-2 significantly raises the levels of neutralizing antibodies against SARS-CoV-2 variants.
Comparative analysis of SARS-CoV-2 isolates uncovers important mutations outside the spike gene that help the Alpha variant to operate under the radar of innate immune surveillance.
On 15–16 November 2021, the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute (NCI) and the National Heart, Lung, and Blood Institute (NHLBI) hosted a virtual workshop on DEAD/DEAH-box RNA helicases in health and disease. The goal of the workshop was to review current advances, and identify knowledge gaps and future research to improve our understanding of the function of RNA helicases, and leverage these molecules as molecular targets with translational potential.
Alveolar macrophages (AMs), the resident macrophages of the lung, can be expanded ex vivo to generate large numbers of cells but show culture adaptations related to epigenetic and transcriptional changes. After transplantation into the lungs of mice, however, culture-expanded AMs lose these adaptations, fully restore in vivo identity and functionally reconstitute the AM pool.
In part of a series of commissioned pieces on coronavirus disease 2019 (COVID-19), Sekaly and colleagues discuss COVID-19 vaccine progress, the underlying biology and prospects for the future.
Delaying a second COVID-19 vaccine dose is a common strategy to maximize vaccine coverage, but the immunological effects are unclear. Hall et al. demonstrate that a delayed second dose significantly enhances neutralizing humoral immunity.
Xue and colleagues show that the transcription factor Tcf1 preprograms a transcriptional program that supports the bioenergetic and proliferative needs of CD8+ central memory T cells in case of a secondary challenge.
Okazaki and colleagues develop and characterize monoclonal antibodies that co-opt T cell PD-1 activity. These antibodies can be used to ameliorate experimental autoimmune disease.
Hayday and colleagues show that sustained Skint1-dependent interactions between murine intraepidermal γδ T cells and keratinocytes are required to maintain the homeostatic barrier function and phenotype of the intraepidermal γδ T cells, including their preparedness to respond appropriately to epidermal challenges.
Although COVID-19 vaccines are proving to be generally effective, new therapeutics to neutralize SARS-CoV-2 are required. Here, the authors engineer bispecific antibodies from ACE2-blocking B38 and H4 SARS-CoV-2 neutralizing antibodies and demonstrate their superiority in mice and nonhuman primates.
Raines et al. examine the role of the PERK-mediated ER stress response in promoting and sustaining M2-like macrophages in type 2 immune response and in tumor immunity.
Sieweke and colleagues show that alveolar macrophages maintain a core gene expression program even after several months in culture and reacquire full transcriptional and epigenetic identity after transplantation into the lung.