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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.
Microglia have key roles in central nervous system (CNS) disease and homeostasis but their study can be challenging. Prinz and colleagues identify hexosaminidase subunit beta (Hexb) to be specifically expressed by microglia and stable even under inflammatory conditions.
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.
Ludewig and colleagues use fate-mapping reporter cells, single-cell RNA-seq analysis and high-resolution microscopy to identify and track the spatial reorganization of follicular reticular cells within germinal centers during the course of an immune response.
Abraham and colleagues show that a highly polarized TH2 bladder response to urinary tract infections promotes epithelial repair at the expense of preventing new infections and associated bladder dysfunction.
Immunoselection underpins tumor antigenic variability and is a key impediment to adoptive cell therapies. Darcy, Beavis and colleagues use T cells engineered to express the dendritic cell growth factor Flt3L to co-opt the host endogenous adaptive immune response and control experimental tumor models.
Tissue-resident memory T (TRM) cells provide rapid front-line protection against infection. Veldhoen and colleagues demonstrate that the type 1 regulatory T cell subset supports generation of TRM cells.
Disulfiram is an FDA-approved drug for treating alcoholism. Wu and colleagues show that disulfiram can be repurposed to efficiently inhibit pyroptosis by specifically blocking gasdermin-mediated pore formation.
Germinal centers are typically divided into dark and light zones. Clark and colleagues identify ‘gray zone’ cyclin B1+ B cell clusters as sites of ongoing cell proliferation, and these cells are distinct from dark zone B cells that undergo AID-dependent somatic hypermutation. This separation of function safeguards B cells undergoing DNA replication against potential mutagenic events that could result in neoplastic transformation.
Myeloid-derived suppressor cells (MDSCs) residing within tumors can impede immune responses. Knolle and colleagues show that MDSCs poison immune cells by producing methylglyoxal, which functionally alters their cellular metabolism and hence their effector responses.
Mildner and colleagues characterize two subsets (Cxcl10+ and Saa3+) of monocytes with pathogenic potential in the central nervous system of mice with experimentally induced autoimmune encephalomyelitis and show these pathogenic cells are not derived from Ly6C+ monocytes, but from early myeloid cell progenitors.