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Plasmacytoid dendritic cells (pDCs) are a major source of type I interferon (IFN-I). Dalod and colleagues show that IFN-I production and T cell activation were performed by the same pDC, but these occurred sequentially and in different micro-anatomical locations during virus infection.
How Lck is recruited to the TCR to initiate signaling is not well known. Here Minguet and colleagues report a previously unknown binding motif in the CD3ε cytoplasmic tail that interacts in a noncanonical mode with the Lck SH3 domain that may help to improve TCR activation and the antitumor activity of a clinically approved CAR.
T cell exhaustion limits antitumor immune responses. Vignali and colleagues identify neuropilin-1 as a novel immune checkpoint that cell-intrinsically operates to limit memory cell formation and can be targeted to enhance antitumor responses.
Gilliet and colleagues demonstrate that skin wound healing occurs through the coordinated action of plasmacytoid dendritic cells, chemokines and skin microbiota.
Thompson and colleagues show that repetitive antigenic stimulation within the tumor environment triggers mitochondrial dysfunction by inhibiting oxidative phosphorylation, which leads to T cell exhaustion.
Van Gisbergen and colleagues show that tissue-resident memory T cells, genetically marked in Hobit reporter mice, can exit tissues upon reinfection and contribute to systemic memory responses.
Geiger and colleagues use SILAC and mass spectrometry to study protein turnover in human T cells and examine how naive T cells maintain their quiescence and transition to activated cells.
Takayanagi and colleagues show that the chromatin remodeler Chd4 works with both Fezf2 and Aire to promote promiscuous tissue-restricted antigen expression in medullary thymic epithelial cells, mediating central tolerance in the thymus.
Familial Mediterranean fever is an autoinflammatory disease caused by gain-of-function mutations in the pyrin inflammasome. Kastner and colleagues show that mutant pyrin better resists suppression by the plague bacterium Yersiniapestis and may have been positively selected in human Middle Eastern populations.
Generation of memory B cells is crucial for protective immunity to infectious agents. Cyster and colleagues show that the transcription factor Hhex interacting with Tle3 promotes memory B cell generation.
Smole and colleagues show that the soluble pattern recognition receptor serum amyloid A (SAA) recognizes several mite allergenic proteins, including Der p 13 and Blo t 13, which are conserved fatty acid-binding proteins. Such FABP–SAA1 binding triggers epithelial cell release of the type-2-promoting cytokine IL-33, which in turn drives IL-13 production and allergic syptoms.
Bcl-6 is the signature transcription factor for TFH cells. Crotty and colleagues provide a comprehensive transcriptional map depicting the regulatory circuitry controlled by Bcl-6 in determining TFH cell fate and function.
Ten–eleven translocation (Tet) enzymes oxidize 5-methylcytosine, facilitating DNA demethylation. Kurosaki and colleagues show that B cell–specific loss of Tet2 and Tet3 leads to lupus-like autoimmunity in mice, in part through increased B cell expression of CD86 and enhanced activation of CD4+ T cells.
Harty and colleagues show that peripheral infections can establish and maintain functional antigen-specific tissue-resident memory CD8+ T cells in the central nervous system.
How lipopolysaccharide embedded in bacterial membranes is sensed by intracellular defense mechanisms has been puzzling. Randow and colleagues show that guanylate-binding proteins assemble on the surface of Gram-negative bacteria to initiate downstream pyroptosis.
Zhao and colleagues show that STING activation is sensitive to membrane lipid peroxidation that occurs upon reactive oxygen species (ROS) production. The lipid hydroperoxidase glutathione peroxidase 4 (GPX4) reduces such oxidized lipids. Lack of GPX4 leads to STING protein carbonylation, which impedes its trafficking from the ER to the Golgi.
Bensinger and colleagues show that interferons promote host cell resistance to bacterial cytolysins by decreasing cholesterol synthesis and promoting the esterification of cholesterol, which alters the availability of this pool of ‘free’ cholesterol needed for pore formation.
Sepsis and physical trauma can increase the susceptibility of patients to pneumonia. Roquilly and colleagues demonstrate that sepsis results in durable impairment of alveolar phagocytic function that is dependent on the localized expression of the inhibitory receptor SIRPα.
NLRP6 is highly expressed in the gut; however, persistent NLRP6 activation can lead to excessive IL-18 production and intestinal bowel disease. Venuprasad and colleagues identify the K63-linked ubiquitin deubiquitinase Cyld as a negative regulator of NLRP6.
Early humoral responses to malaria fail to induce durable protective antibodies. Butler and colleagues report that low-affinity, short-lived plasmablasts become nutrient sinks for glutamine and starve germinal center B and T cells, thereby reducing the generation of high-affinity B cells and long-lived plasma cells and memory B cells.