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Adaptation to hypoxia and immune escape are two hallmarks of Mycobacterium tuberculosis infection. The d-serine isomer has now been identified as a factor produced by M. tuberculosis upon hypoxic conditions, dampening CD8+ T cell responses.
The developmental relationship between natural killer (NK) cells and other innate lymphoid cells (ILCs) has been a subject of scrutiny in recent years. Two studies now identify an early precursor committed to the NK cell lineage.
Bhandoola and colleagues describe the existence of two pathways of NK cell development that generate functionally distinct NK cell subsets in mice, and which may be conserved in humans.
Immune responses are subject to circadian regulation, but circadian effects on antitumor immune response are unknown. Disruption of intestinal circadian rhythms is now shown to promote immunosuppression by altering the tumor immune microenvironment (TIME) in colorectal cancer.
Shlomchik and colleagues uncover a positive feedback loop between interleukin-12 and interferon-γ, which promotes extrafollicular plasmablast differentiation and suppresses germinal center formation.
Dendritic cells experience cell shape changes while migrating within the complex physical environment of tissues. Sensing of these shape changes modifies their migratory properties and imprints these cells with immunoregulatory properties.
Genetic lineage tracing and progenitor and multilineage fate mapping after single hematopoietic stem cell (HSC) transplantations identify two distinct HSC-progenitor trajectories for the replenishment of platelets in mice. These pathways include a slower multilineage pathway and a faster platelet-restricted or biased pathway, initiated by distinct and non-hierarchically related HSCs.
This work identifies two rare genetic variants of UNC93B1 that contribute to the development of childhood-onset lupus. Mice that expressed one of these variants developed a lupus-like disease. UNC93B1 is known to regulate the localization of Toll-like receptors (TLRs) to the endosome, and UNC93B1 variants resulted in enhanced responses to TLR7 and TLR8 agonists.
Here the authors show that BTLA on effector T cells interacts with HVEM on other immunosuppressive cells in the tumor microenvironment. The authors also present evidence that overcoming this checkpoint can ehance CAR T functionality.
Structure-guided protein design enables germline-targeting immunization strategies to generate broadly neutralizing antibodies against MPER, a region of the HIV envelope glycoprotein that is functionally important and highly conserved, but a challenging target for antibody responses.
Batista, Schief and colleagues use a series of germline-targeting immunogens in knock-in mice expressing heavy chain sequences derived from the HIV broadly neutralizing antibody 10E8 to characterize the requirements of 10E8 B cell precursors for entry and maturation in the germinal center.
Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.