Volume 21 Issue 10, October 2020

New studies suggest that NKG7 is essential for NK and CD8⁺ T cell cytotoxic degranulation and CD4⁺ T cell activation and proinflammatory responses. While the mechanism is yet to be determined, the functional relevance is exciting and opens the possibility of a new target for cellular immunotherapies.

Costimulatory blockade via the CTLA-4–Ig fusion protein abatacept is beneficial in patients with early-onset type 1 diabetes, but some individuals benefit more than others. A new study reports that the pretreatment abundance of T follicular helper (T_FH) cells could predict clinical responses to abatacept.

A vicious cycle, linking obesity with chronic inflammation, fuels the development and exacerbation of metabolic syndrome and other disorders. Modulation of mitochondrial energy metabolism via interleukin-1β signaling establishes a runaway positive-feedback loop that brings about and reinforces the sequelae of a high-fat diet.

“The role of cytokines in COVID-19” online symposium was presented on 18 June 2020 by the NIH/FDA Immunology and Cytokine Interest Groups and was purposed to discuss our rapidly changing understanding of COVID-19-related cytokine responses in different stages of infection, including the etiologies, downstream consequences and possible mitigation strategies. The recording is available at https://nci.rev.vbrick.com/sharevideo/03106730-66cc-47ba-870b-f6e6274a998a.

Pancreatic cancer has one of the worst survival outcomes of all cancers. Leinwand and Miller review the immunological landscape of pancreatic cancer, immune evasion mechanisms and the impact of the microbiota.

Autophagy controls cellular homeostasis and influences immune responses. Galluzzi and colleagues show that tumor cell autophagy opposes inflammatory cell death following radiation therapy and can be inhibited to enhance antitumor responses.

Takayanagi and colleagues show that thymic medullary fibroblasts can contribute to central tolerance mechanisms by expressing cell-type-specific antigens distinct from those expressed by medullary thymic epithelial cells.

Siracusa and colleagues reveal a regulatory role for basophils in the context of anti-helminth immunity and identify the neuropeptide neuromedin B as a potent inhibitor of type 2 inflammation.

Williams and colleagues investigate the origin, dynamics and transcriptional profiles of aortic intima macrophages during atherosclerosis disease progression.

NKG7 is a molecule well associated with NK cells but of unknown function. Engwerda and colleagues demonstrate that NKG7 is also associated with T_H1 cells and is essential for type I and cytotoxic responses.

Obesity is often accompanied by chronic inflammation. Li and colleagues show that, in mice fed high-fat diets, IL-1 signaling in adipocytes induces an unconventional IRAK2 translocation to mitochondria and suppresses respiratory super-complex formation to alter mitochondrial function, and exacerbates obesity.

The adhesion receptor CD2 plays an important role in the full activation of T cells. Dustin and colleagues show that CD2 occupies a region in the periphery of the immunological synapse where it amplifies cognate antigen signals, whereas the presence of PD-1 disrupts this effect.

The CTLA-4–Ig fusion protein (abatacept) can have beneficial effects in autoimmune disease. Walker and colleagues show in mouse and human type 1 diabetes that abatacept targets pathogenic follicular helper T cells, and the frequencies of these cells at baseline can be used to stratify treatment responses in patients.

The developmental timing for exhaustion is still obscure. Kallies and colleagues demonstrate that CD8⁺ T cell ‘exhaustion’ actually begins in the less-differentiated TCF1⁺ ‘precursor’ T cell pool during chronic viral infections.

Antigen-activated B cells are short lived in the absence of a second signal provided by CD4⁺ T cells or cytokines. Zikherman and colleagues report that the NR4A family of nuclear receptors (NUR77 and NOR-1) are responsible for enforcing this ‘tolerance’ to self-antigen (signal 1 only) and explain, in part, why B cells are dependent upon a second signal.

The epigenetic landscape of human αβ and γδT cell development has remained unexplored thus far. Taghon and colleagues provide a resource of RNA-seq and ATAC–seq profiles examining human thymocyte development.

Accurate serology testing is urgently needed to help diagnose SARS-CoV-2 infection. Here Valkenburg and colleagues use a luciferase immunoprecipitation system to assess the antibody responses to 15 different SARS-CoV-2 antigens in patients with COVID-19 and find ORF8 and ORF3b antibodies, taken together as a cluster of points, identified 96.5% of COVID-19 samples at early and late time points of disease with 99.5% specificity