News & Views in 2021

Zhong et al. exploit allelic variations in mice to pinpoint the ‘heavy lifter’ transcription factor families governing the chromatin landscape of resting and activated T cells.

New data show that, compared with adults, children infected by SARS-CoV-2 preferentially activate pre-existing immunity to endemic common-cold coronaviruses that are cross-reactive with SARS-CoV-2, with potential implications for pediatric vaccine strategies.

New research provides evidence of an impaired vitamin D gene signature in CD4⁺ T cells in patients with severe COVID-19. Mechanistically, it is shown that vitamin D alters the epigenetic landscape of CD4⁺ T cells, as well as inducing key transcription factors such as STAT3, BACH2 and JUN that reduce levels of IFN-γ and increase IL-10. These changes generate pro-resolving T_H1 cells that may be beneficial in resolving or preventing severe COVID-19.

Chronic viral infections can trigger ineffective antibody responses. A new study shows that deletion of B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) from B cells restores protective antibodies during chronic infection.

In patients with rheumatoid arthritis, a short supply of aspartate in the mitochondria can force the endoplasmic reticulum of T cells to generate transmembrane TNF, which in turn contributes to synovial inflammation.

Analysis of antibody responses in BCG intravenous vaccination against Mycobacterium tuberculosis in non-human primates show a potential protective role for IgM.

Whether COVID-19 during pregnancy affects the health of children is unclear. Data now show that SARS-CoV-2 infection of mothers can prime the fetal immune response indirectly even when the virus does not infect the fetus.

When transformed cells emerge in an epithelium, their elevated class I MHC expression signals to normal neighboring epithelial cells, which respond by inducing their apical extrusion as a tumor-suppressive mechanism.

Thrombosis complicates SARS-CoV-2 infection and vaccination. Recent data are being used to identify the autoimmune antibody repertoires responsible for the excessive activation of coagulation and platelets.

During acute COVID-19, there is little correlation between the nose and blood in terms of antibodies or cytokines; instead, these factors are associated with nasal microbiota.

Conjugation of the ubiquitin-like protein ISG15 to targets (ISGylation) benefits antiviral defense. However, SARS-CoV-2 induces human macrophages to preferentially secrete ISG15 via its papain-like protease, and extracellular non-conjugated ISG15 acts as a cytokine to exacerbate SARS-CoV-2-triggered inflammation.

The retention of erythroid mitochondria, a feature associated with impairments in the ubiquitin–proteasome system, is detected in a subset of pediatric patients with lupus and is associated with the type I interferon pathway.

Infections are known to induce epigenetic rewiring in myeloid cells, a phenomenon known as trained immunity, which protects against re-infection. New data show that, in mice, trained immunity can be inherited, possibly by gametic DNA methylation and chromatin remodeling linked to immune traits.

Type I interferon response to systemic infections after head trauma or stroke impairs angiogenesis in injured tissues and may contribute to secondary neurological injury.

Qiu and colleagues identify IRX3 as a driver of macrophage inflammatory cytokines, which can promote metabolic dysfunction.

Systems approaches applied to human and nonhuman primate cohorts revealed that the transcription factor CREB1 (cAMP-responsive element-binding protein 1) may be a key driver of human immunodeficiency virus 1 vaccine-induced immunity.

Environmental allergens trigger activation of the ripoptosome in epithelial cells, which mediates the initial allergic response via intracellular processing and release of the alarmin IL-33 and represents a newly identified mechanism for epithelial allergen sensing.

Corbett et al. use the rhesus macaque model to evaluate the ability of the mRNA-1273 (Moderna) COVID-19 vaccine to protect against challenge with the antibody-evading Beta variant of SARS-CoV-2. Their key finding is that the vaccine prevents severe lung pathology, principally because it is able to induce a strong enough antibody resistance to overcome the variant’s relative resistance.

CD8⁺ resident memory T (T_RM) cells from different tissues form a heterogeneous population. Transforming growth factor (TGF)-β-independent CD103^– T_RM cells in the liver retain the ability to move to barrier tissues or return to secondary lymphoid organs.

Autoimmune inflammation and disease creates an environment that results in defective regulatory T (T_reg) cell functions. New data show how induction of Foxp3 expression in these T_reg cells during ongoing autoimmune inflammation can restore control over pathogenic T cell functions and resolve inflammation and pathology in mice.