Volume 21 Issue 12, December 2020

Anjana Rao describes the team effort to define the changes in chromatin accessibility in naive T cells during T_H1 and T_H2 cell differentiation after stimulation with TCR ligands and the appropriate cytokines. Her lab showed that differentiated T_H1 and T_H2 cells, which produce the cytokines IFN-γ and IL-4, respectively, displayed distinct patterns of DNase I hypersensitivity, histone acetylation and NFAT1 transcription factor binding around the Ifng and Il4 genes. This project turned them into a ‘real’ immunology lab!

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

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.

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.

Segal and colleagues identify a neuroprotective immature-like neutrophil subset that participates in dectin-1-dependent axon repair and regeneration in the central nervous system.

Sanz and colleagues examine B cell subsets in a cohort of patients with COVID-19. Severely ill patients have higher frequencies of activated extrafollicular T-bet⁺ B cells that form antibody-secreting cells, the majority of which express germline sequences and are reminiscent of antibody responses observed in patients with systemic lupus erythematosus during flares.

Within a human cohort, wide variation can occur with constitutively expressed proteins. Aschenbrenner and colleagues found that individuals with lower CRELD1 expression have decreased frequencies of naive CD4⁺ T cells. Mice with conditional Creld1 deficiency also exhibit a phenotype associated with immunological aging.

Humans with inherited defects in DOCK8 expression are prone to allergic, type 2 CD4⁺ T cell responses. Mandl and colleagues reveal an important role for cell death in driving such type 2 signals during infection.

Ho and colleagues report that mitochondrial dysfunction and impaired mitophagy triggered by the tumor microenvironment lead to subsequent epigenetic changes and cause permanent T cell exhaustion and dysfunction.

The identity of stem-cell memory progenitor cells has been unclear. Lugli and colleagues use high-dimensional approaches to identify two new progenitor populations of human T cells—one giving rise to a functional lineage, the other to an exhausted-like one.

T cell memory formation is often described as occurring during the chronic phases of infection. Buchholz and colleagues use the phenomenon of ‘memory inflation’ following cytomegalovirus infection to show that a tiny subset of self-renewing T cells branch off early from the bulk population to generate memory.

Exploring transcriptional heterogeneity of cKit⁺Sca1⁺ HSPCs using single cell RNA-sequencing, Naik and colleagues identify a population termed ‘lymphoid primed progenitors’ as the earliest stage of lymphoid lineage commitment, marked by downregulation of the stem/myeloid transcription factor Dach1.

Sepsis is a biphasic disease characterized by an initial inflammatory phase, followed by a prolonged immunosuppression phase. Puthalakath and colleagues utilize a CRISPR-mediated mutagenesis screen to identify TREML4 as a regulator of sepsis-induced immunosuppression.

CD4⁺ T cells are critical for effective responses to infection with the malaria parasite. Haque and colleagues use single-cell RNA sequencing and computational modeling to track T cell memory development during experimental Plasmodium infection of mice.