Volume 22 Issue 9, September 2021

Like other countries in the region, the United Arab Emirates (UAE) was deeply affected by the pandemic. However, its foresight and proactive policies helped to create opportunities out of the challenges and spurred the development of trilateral collaborations involving government, academia and industry.

One year into the COVID-19 pandemic, governments and health agencies are hyperfocused on mitigation efforts such as masking and physical distancing, as well as vaccine logistics—as they should be. But they continue to ignore, much to everyone’s peril, a parallel, ever-worsening public health crisis: the damage done by the spread of medical mis- and disinformation online.

Analysis of the transcriptional landscape of inflammatory neutrophils discloses specific transcription factor engagement at the bone marrow–to-blood and the blood-to-tissue transitions.

Inhibition of ferroptosis via selenium supplementation promotes the survival of follicular helper T cells, boosting the germinal center and antibody response following vaccination in mice and people.

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.

Tissue-resident alveolar macrophages promote early tumor invasiveness and induction of immunosuppressive regulatory T cells in non-small cell lung carcinoma.

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.

Schwartz and colleagues review the immune niches in the brain, the contribution of professional immune cells to brain functions and the relevance of immune components to brain aging and neurodegenerative disease.

Neutrophils demonstrate highly dynamic functional and transcriptional changes depending on their tissue environment. Udalova and colleagues use an inflammation model to examine neutrophils and find that the transcription factors RUNX1 and KLF6 control maturation; RELB, IRF5 and JUNB drive effector responses; and RFX2 and RELB promote survival.

Zhang and colleagues identify a role for cell death by glutathione peroxidase 4 (GPX4)-regulated ferroptosis in neutrophils from patients with systemic lupus erythematosus, which is triggered by type I interferons and autoreactive antibodies and contributes to lupus pathogenesis. Inhibiting accumulation of oxidative mediators by GPX4 suppresses ferroptosis.

Lucas and colleagues describe loss-of-function variants in the X-linked ETS transcription factor ELF4 in multiple unrelated male patients with early onset mucosal autoinflammation and inflammatory bowel disease (IBD)-like features.

T follicular helper (T_FH) cells are important for the generation of effective antibody responses. Yu and colleagues find that T_FH cells are exceptionally sensitive to death by ferroptosis and that this process is regulated by the activity of the selenoenzyme GPX4.

Tissue-resident memory T (T_RM) cells are distributed throughout the body as relatively sessile populations. Mackay and colleagues find that the tissue in which T_RM cells are generated dictates their properties and is in turn defined according to T_RM-cell-intrinsic sensitivity to signaling via the cytokine TGFβ.

Khazaie and colleagues show that TCF-1 cooperates with FOXP3 to differentially regulate independent suppressive activities of T_reg cells. T_reg cell–specific deficiency of TCF-1 increases tumor load in mice predisposed to polyposis. Functionally, TCF-1-deficient T_reg cells suppress viral antigen–specific CD8⁺ T cell cytotoxicity, but TCF-1-deficient T_reg cells fail to suppress T_H1 or T_H17 polarization of conventional CD4⁺ T cells. This scenario leads to increased cytokine-mediated tissue inflammation but still restrains the adaptive antitumor cytotoxicity.

Regulatory T cells are functional in a broad-spectrum systemic autoimmune disease and are capable of suppressing innate and adaptive immune responses, reversing established tissue inflammation and enabling long-term restoration of immunological health.

Adipose tissue-resident regulatory T (T_reg) cells are important for maintaining normal metabolic function and adiposity. Li and colleagues demonstrate that insulin signaling directly controls adipose T_reg cell development and functionality