Reviews & Analysis

Injury or infection renders patients vulnerable to secondary pneumonia. A new study indicates that SIRP-α triggers prolonged impairment of the phagocytic capacity of alveolar macrophages after the resolution of primary bacterial or viral pneumonia.

Tsokos reviews how the genetic, epigenetic and microbial environments influence innate and adaptive immune cells to drive immunopathology and organ damage in systemic lupus erythematosus.

Myeloid-derived suppressor cells (MDSCs) occupy sites of chronic inflammation and suppress CD8⁺ T cell function. A new study describes the transfer of the metabolite methylglyoxal (MG) to T cells, which mediates this immunosuppressive mechanism.

Single-cell RNA-sequencing of myeloid cells during neuroinflammation identifies a new population of pathogenic Cxcl10-expressing phagocytes, which develop independently of Ly6C^hi monocytes but derive from early myeloid precursors shaped by the inflamed tissue microenvironment.

Activation of TLR–TRAF6 signaling by chronic inflammation in myelodysplastic syndromes increases the competitive advantage of HSPCs harboring MDS mutations through the upregulation of the ubiquitin-modifying enzyme A20 and a switch from canonical to non-canonical NF-κB signaling.

Oxidative stress is an imbalance in the production of reactive oxygen species and the ability to remove or detoxify these molecules, which causes cellular damage. Leveraging novel sequencing methods and high-throughput screens leads to the discovery of possible new therapies.

CD8 memory–phenotype differentiation is a T cell antigen receptor–governed process that begins in Eomes⁺ thymic precursors and is subsequently completed in the periphery. These CD8-MP cells can infiltrate tumors, where they express PD-1.

The RNA modification N⁶-methyladenosine (m⁶A) plays an essential role in the regulation of immunity. Here, Shulman and Stern-Ginossar review the roles of m⁶A in controlling immune recognition, activation of innate and adaptive immune responses, and cell fate decisions.

Epigenetic modifications are associated with distinct stages of autoreactive CD8⁺ T cell differentiation. DNA methylation and chromatin changes guide the acquisition of a memory-like phenotype and sustain prolonged autoimmune effector responses.

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.

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.

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.

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.

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.

Schwartzberg and colleagues discuss the advances and challenges for female scientists working in the field of immunology at the US NIH.

Chronic inflammation associated with HIV-1 infection disrupts the homeostasis of gut-resident innate lymphoid cells and induces the generation and expansion of adaptive NK cells expressing TCF7, a transcription factor that sustains their effector functions and memory-like properties.

Regulatory T (T_reg) cells suppress antitumor immunity, but T_reg cell inhibition has been hampered by a lack of specific targets. CD36 expression by tumor-infiltrating T_reg cells may provide a way to specifically target T_reg cells in tumors.

Highly proliferative cells have classically been thought to rely on anaerobic glycolysis for fuel. Weisel et al. show that germinal center B cells break this rule, as they primarily utilize fatty acid oxidation to meet their metabolic demands.

Oxidative stress in the tumor microenvironment activates expression of the phosphatase PAC1 in infiltrated T lymphocytes. PAC1 regulates the epigenetic modulator NuRD to limit the chromatin accessibility of T cell effector function genes, thereby fostering T cell exhaustion.