Volume 21 Issue 4, April 2020

Immunological memory is a crucial feature of adaptive immunity. A new report proposes a novel ‘outside-in’ mechanism by which a recall immune response may be initiated from the tissue, rather than secondary lymphoid organs.

Comprehensive analysis of CD8⁺ T cell populations specific to cytomegalovirus reveals that the evolution of the T cell antigen receptor repertoire during chronic infections is characterized by the expansion of low-affinity clones.

The ubiquitin-editing enzyme A20 has a pivotal role in restricting autoimmune and inflammatory responses. New studies suggest that A20 prevents inflammatory diseases using a non-catalytic mechanism involving ubiquitin binding.

PD-L1 expressed by T cells provides backward and forward signals to restrain both innate and adaptive immune responses in tumor tissues.

γδ T cells are critical contributors to tissue homeostasis. Recent research identifies an unexpected role for γδ T cell–derived IL-17F in promoting sympathetic innervation and tissue thermogenesis through the induction of the cytokine TGF-β in adipose cells.

Turley and Krishnamurty review new insights into lymph node stromal cells, a heterogeneous cell population that serves distinct functions during development, in maintaining lymphocyte homeostasis, and in coordinating immune responses.

van Loo and colleagues provide insights into the action of the anti-inflammatory protein A20. The ZnF7 and ZnF4 ubiquitin-binding domains of A20 are both required to suppress inflammatory signaling and cell death; however, these zinc fingers operate via distinct mechanisms.

Monticelli and colleagues analyze primary human CD4⁺ T cells to interrogate gene expression regulatory pathways that distinguish GM-CSF⁺ pathogenic programs from noninflammatory programs. They identify the transcriptional repressor BHLHE40 as an enforcer of proinflammatory gene expression by suppressing the NF-κB inhibitor miR-146a and the RNase ZC3H12D.

Mucosal-associated invariant T (MAIT) cells recognize vitamin B metabolites presented by the molecule MR1. Rossjohn and colleagues generate multiple altered metabolite ligands and determine their structures in the context of MR1 and the TCR to develop a generalized framework for MAIT cell antigen recognition.

Tissue-resident memory (T_RM) cells are generally stably maintained in discrete tissues or organs. Masopust and colleagues show that T_RM cells can reenter the circulation, and exhibit considerable plasticity, although they retain a proclivity to reestablish themselves in their tissue of origin.

The deubiquitinase A20 is a potent inhibitor of NF-κB signaling pathways. Ma and colleagues identify distinct roles for A20 ubiquitin-binding ZF4 and ZF7 domains, which exhibit different phenotypes upon mutation, but play synergistic roles in regulating inflammatory responses.

Busch and colleagues use single-cell and bulk TCR sequencing and structural affinity analyses of CMV-specific T cells to show that the immunodominance of high-affinity T cell clones declines during chronic infection with CMV, likely due to cellular senescence.

PD-L1 on tumor cells exerts an important dampening effect on T cells via their expression of PD-1. Miller and colleagues find that PD-L1 ‘back-signaling’ into T cells and macrophages can also dampen immune responses within the tumor microenvironment.

Unanue and colleagues examine the immunopeptidome of pancreatic islets in non-obese diabetic (NOD) mice, which spontaneously develop autoimmune diabetes, to reveal the key features of a restricted component in the self-MHC-II peptidome that causes autoreactivity.

The pathobiological validity of mouse models of mycobacteria infection is sometimes questioned. O’Garra and colleagues demonstrate that mice share transcriptomic modules with active human tuberculosis and a characteristic type I IFN signature.