Volume 22 Issue 2, February 2021

Single-cell-sequencing techniques enable the decades-old T helper subset dogma to be re-examined in an unsupervised manner, bringing nuance to the definition of known subsets while simultaneously identifying interesting new cell states.

A new study shows successful immunotherapy of a detrimental gastrointestinal disease using the complement inhibitor eculizumab.

Following internalization of an actin-bearing ligand, the C-type lectin receptor DNGR-1 promotes phagosome rupture, allowing antigens to access the cytosol and be processed through the MHC-I pathway.

Animal models provide invaluable insights into the functioning of the immune system; however, they have their limitations. In a Perspective, Andrea Graham argues that using a more naturalized biotic and abiotic setting can help capture a more accurate picture of the immune system.

Based on the results of recent studies that have dissected the response of individual macrophage subsets to pulmonary insults, Guilliams and Svedberg call for an adjustment of the macrophage plasticity concept.

CHAPLE disease is a lethal syndrome caused by genetic loss of the complement regulatory protein CD55. Lenardo, Ozen and their colleagues report that blockade of C5 complement activation in a small cohort of pediatric patients with CHAPLE disease reduced gastrointestinal pathology and restored their immunity and growth.

The mechanism by which ingested material accesses the cytosol for cross-presentation is unclear. Caetano Reis e Sousa and colleagues demonstrate that signaling via the lectin receptor DNGR-1 ruptures the phagosome and releases its contents to the cytosol for cross-presentation.

Damage-associated molecular patterns (DAMPs) are released during necrotic cell death and contribute to driving inflammation. Rathinam and colleagues show that galectin-1 is a new DAMP that functions by inhibiting the receptor phosphatase CD45.

McKenzie and colleagues show RORα expression in early thymic progenitors overrides BCL11B-dependent suppression of Id2 and Nfil3 expression. In turn, ID2 suppresses the activity of the E proteins that are required for T lineage development, thereby promoting ILC2 cell generation in the thymus.

γδ T cells have potent effector functions through their production of IFN-γ or IL-17. Pennington and colleagues demonstrate that IFN-γ⁺ γδ T and IL-17⁺ γδ T cells have distinct metabolic requirements that can be independently targeted to elicit specific immune responses.

Metabolic rewiring of cytotoxic T lymphocytes (CTLs) can impair their antitumor functions. Sun and colleagues demonstrate that CTL-intrinsic activity of the kinase NIK is essential for CTL metabolic fitness in the tumor microenvironment.

Delgoffe and colleagues show that continuous TCR signaling and hypoxia increase Blimp-1, which suppresses PGC-1α-dependent mitochondrial reprogramming and increases reactive oxygen species generation. Such conditions promote T cell exhaustion.

Helper T cell subsets are characterized functionally by the cytokines they produce. Benoist and colleagues demonstrate that in vivo helper T cells do not manifest as discrete helper subsets but rather form a continuum shaped by microbial exposure.

Thimme and colleagues identify a molecular signature of T cell exhaustion resembling a ‘chronic scar’ that is imprinted in hepatitis C virus–specific CD8⁺ T cells and cannot simply be reversed by viral clearance.

Melnick and colleagues show that the cohesin complex exhibits dose-dependent regulation of chromatin remodeling that accompanies the transition of germinal center B cells to plasma cells, which is necessary to prevent lymphomagenesis.