Volume 22 Issue 11, November 2021

If new treatments for immune-mediated inflammatory diseases (IMIDs) are to emerge, then a radical new approach that moves the field from one that is based on clinical signs and symptoms to one that is based on immunological and molecular mechanisms is urgently needed. This requires a new way of thinking: that IMIDs should be approached as having shared common pathogenic cells and pathways, and that therapies should be targeted at these cells and processes rather than clinical features.

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.

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.

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.

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.

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.

On 27 ̶ 29 July 2021, the National Institute of Allergy and Infectious Diseases (NIAID) hosted a virtual workshop on the topic of secondary vaccine effects to discuss existing evidence, potential immunological mechanisms and associated public health implications.

ILC2 metabolism has been largely unexplored. Di Santo and colleagues examine metabolic profiles from naive and cytokine-activated ILC2s and find that IL-33-triggered ILC2s rely on distinct metabolic pathways to sustain proliferation and function.

Scheiermann and colleagues show that circadian clocks control the infiltration of dendritic cells into skin lymphatics in mice and humans, with a peak migration to the lymph nodes during the rest phase.

Transgenerational transmission of acquired immunological traits has been demonstrated in invertebrates and plants but not mammals. Katzmarski et al. demonstrate that trained immunity that protects against heterologous infections can be transmitted to F2 offspring.

Epithelial cells can use an immune-like mechanism to extrude neighboring precancerous cells; however, the recognition and control mechanisms of this process are unclear. Maruyama and colleagues demonstrate that LILRB3 on normal epithelial cells recognizes elevated MHC class I on transformed cells and triggers the extrusion process.

Tumor-associated macrophages support an immunosuppressive tumor microenvironment. Di Conza et al. uncover how IRE1–XBP1 and IRE1−STAT3 endoplasmic reticulum stress responses pathways are engaged by tumor-derived lipids to orchestrate pro-tumorigenic features and survival in tumor-associated macrophages.

The antiviral factor ISG15 can be conjugated to other proteins through ISGylation. Sanyal and colleagues find that viruses can modulate ISGylation, which in turn alters macrophage responses and can result in exaggerated inflammation in COVID-19.

Mucosal surfaces of the respiratory tract are the first sites of entry and defense against SARS-CoV-2. Di Santo and colleagues perform paired analysis of the nasopharyngeal and systemic immune responses of SARS-CoV-2-infected patients and demonstrate distinct compartmentalization of immunity and shifts in the microbiome.

Intestinal epithelial cell (IEC) damage by T cells contributes to alloimmune, autoimmune and iatrogenic diseases such as graft-versus-host and inflammatory bowel disease. Here the authors identify a critical role for the alteration of the IEC-specific mitochondrial complex II component succinate dehydrogenase A in the regulation of the severity of T cell-mediated intestinal diseases.

Pediatric COVID-19 can be associated with subsequent multisystem inflammatory syndrome in children (MIS-C), but how these pathologies are related or differ is unclear. Here the authors compare and contrast pediatric COVID-19 and MIS-C immunophenotypes using SARS-CoV-2 antibody fingerprinting proteomics.