Reviews & Analysis

Weyand and Goronzy discuss how the progressive loss of immune cell tolerance underlies the immunopathology associated with rheumatoid arthritis.

Comprehensive analysis of specific and cross-reactive SARS-CoV-2 epitopes reveals functional T cell responses against specific viral regions in essentially all convalescent individuals and a majority of unexposed donors, demonstrating that cross-reactive responses to COVID-19 are widespread.

The natural variability of CRELD1 expression identified in comprehensive data sets from healthy individuals helps predict and establish its role in regulating T cell homeostasis.

A subset of neutrophils with an immature phenotype confers neuroprotection in traumatic optic nerve and spinal cord injury. This study identifies a new target population of cells for therapeutic strategies to induce neural regeneration during injury.

An exaggerated extrafollicular B cell response characteristic of active systemic lupus erythematosus also characterizes the B cell response to SARS-CoV-2 in those with severe COVID-19.

The presence of central memory precursor cells during the acute response to cytomegalovirus infection is the best predictor of whether a T cell family will contribute to the inflationary memory pool.

In contrast with the classical dogma that the pathways generating either memory or ‘exhausted’ T cells are strictly segregated, data now identify a clonally distinct hybrid memory T cell subpopulation with an exhausted phenotype.

Terrando and colleagues review key mechanisms related to postoperative inflammation and the implications for developing perioperative neurocognitive disorders, with a focus on neuroinflammation and key cellular targets affected by surgical trauma.

Exposure to environmental pollutants can lead to immune system dysfunction with severe pathological consequences. Yamamoto and colleagues review the impact of pollutants on immune function and describe potential means to ameliorate these effects.

The lung endothelial cell–derived angiocrine Rspondin3 activates Wnt–β-catenin signaling in interstitial macrophages, leading to a metabolic–epigenetic reprogramming of interstitial macrophages that drives anti-inflammatory responses and attenuates endotoxin-induced lung injury.

Two studies reveal a role for the transcriptional regulator BATF3 as a T cell–intrinsic factor mediating effective memory responses. This finding opens future avenues of investigation and opportunities to enhance cellular immunotherapy.

The mechanisms that drive responses to PD-1-blocking immunotherapy in some but not all patients have been puzzling. A new study suggests that the balance of PD-1 expression levels between CD8⁺ T cells and T_reg cells might provide an answer.

The activation of the Notch4–Wnt–GDF15 axis in induced regulatory T (T_reg cells) dampens their immunoregulatory function and turns them into T_H2 and T_H17 cytokine producers, allowing them to maintain ongoing allergic asthma.

Cytokines are well-known mediators of the immune response, but, recently, pleiotropic roles in the central nervous system have started to be uncovered. It is now shown that IL-17 directly modulates fear behavior in mice.

Comprehensive mapping reveals that functional CD4⁺ and CD8⁺ T cells targeting multiple regions of SARS-CoV-2 are maintained in the resolution phase of both mild and severe COVID-19, and their magnitude correlates with the antibody response.

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.

To trigger an adequate humoral immune response while ensuring self-tolerance, B cell activation is tightly controlled. A new study indicates that an NR4A-enforced built-in brake fine-tunes the early phase of transcriptional reprogramming induced by BCR stimulation.

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.

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.