Volume 22 Issue 7, July 2021

SARS-CoV-2 infection activates TLR2 signaling, which results in the robust expression of proinflammatory cytokines that may contribute to disease in severe COVID-19. Inhibition of this signaling pathway represents a potential target for COVID-19 therapeutics.

Effective anticancer adoptive cellular therapy (ACT) requires sufficient infiltration of injected cytotoxic lymphocytes, but pathophysiology frustrates this. Regulator of G protein signaling 1 limits T cell trafficking to breast tumors and may be targeted to improve ACT.

The role of type 2 innate lymphoid cells (ILC2s) in cancer is currently under substantial scrutiny. New data show that ILC2s producing the proinflammatory cytokine GM-CSF coordinate eosinophils’ recruitment and activation to enhance antitumor responses

A multimodal proteomic analysis of the perturbations that SARS-CoV-2 and SARS-CoV induce in infected human lung epithelial cells reveals common and distinct immune-evasive and pathobiological mechanisms used by these coronaviruses.

Sharpe and colleagues review salient aspects of CD8⁺ T cell dysfunction in cancer, chronic viral infections and autoimmunity, with a view of developing new ways to alleviate T cell exhaustion and enhance CD8⁺ T cell functions in cancer and chronic viral infection, as well as strategies to induce or augment exhaustion-like features to treat autoimmunity.

RIG-I is a cytosolic nucleic acid sensor triggering type I IFN production. Takaoka and colleagues find that RIG-I recognizes SARS-CoV-2 RNA in a noncanonical manner and fails to activate type I IFN, but it directly restricts viral replication.

The innate sensors of SARS-CoV-2 are still being determined. Kanneganti and colleagues find that SARS-CoV-2 envelope protein is sensed by TLR2 and this drives pathogenic inflammatory cytokine production.

Modlin and colleagues examined the skin lesions of human leprosy patients using single-cell RNA sequencing coupled to cellular spatial mapping. Their analysis maps the architecture of granulomas in leprosy lesions from patients with leprosy with localized disease (tuberculoid leprosy, reversal reaction) to those with progressive infection (lepromatous leprosy).

Group 2 innate lymphoid cells (ILC2s) are generally considered to have pro-tumor functions. However, Belz and colleagues demonstrate that ILC2s have anti-melanoma effects due to their high production of the inflammatory cytokine granulocyte-macrophage colony-stimulating factor in the tumor microenvironment.

Effective control of tumors requires the presence of inflammatory helper and cytotoxic T cells. Song and colleagues demonstrate that the protein RGS1 cell-intrinsically regulates effector T cell homing to tumors and thereby impairs tumor control.

Korn and colleagues demonstrate that the site of T cell priming (gut versus skin draining lymph nodes) dictates their effector phenotypes and homing to distal sites of immunopathology.

The zinc-finger transcription factor IKAROS is essential for B cell development. Taniuchi, Morio and colleagues identify a human kindred presenting with B cell immunodeficiency that was caused by a heterozygous missense mutation in IKZF3 encoding the related AIOLOS protein. AIOLOS^G159R is a mutant protein that interferes with both wild-type AIOLOS and IKAROS by forming heterodimers that bind to aberrant DNA-binding sites and prevent normal expression of IKAROS-dependent genes.

Xu and colleagues use single-cell transcriptomic analyses to uncover distinct expression dynamics of metabolic programs in germinal center B cells. Coupled analysis of transcriptional states and Igh variable sequences revealed that OXPHOS metabolism is enhanced in GC B cells undergoing positive selection. Their findings suggest BCR signaling tunes GC B cell metabolism to accelerate the cell cycle of positively selected GC B cells.

Brown and colleagues generated an atlas of miRNA expression profiles from primary mouse immune cell populations and connected these signatures with ATAC–seq, ChIP–seq and nascent RNA profiles to establish a map of miRNA promoter and enhancer usage in immune cells.