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Germinal center B cells can undergo rapid proliferation. Shlomchik and colleagues show that germinal center B cells, unlike other rapidly proliferating cells, do not depend on glycolysis, but rather increase their peroxisome content and rewire their cellular metabolism to exclusively utilize fatty acid oxidation for their energetic needs.
HIV-1 infection is associated with persistent inflammation that can contribute to a variety of comorbidities. Luban and colleagues demonstrate that HIV-1 infection results in permanent depletion of innate lymphoid cells, leading to breakdown of gut barrier function and a feed-forward inflammation loop, which includes skewing of NK cells toward an inflammatory/memory phenotype.
Tumor environments are highly acidic due to high concentrations of lactic acid. Ho and colleagues report that tumor-infiltrating regulatory T cells adapt to this tumor environment by upregulating expression of CD36, which allows them to use fatty acids to fuel their metabolism.
Iannacone and colleagues show that the spatiotemporal regulation of type I interferon expression shapes the differentiation of antiviral CD4+ T cells into TFH or TH1 cells.
Tissue-resident memory (TRM) cells are generally stably maintained in discrete tissues or organs. Masopust and colleagues show that TRM cells can reenter the circulation, and exhibit considerable plasticity, although they retain a proclivity to reestablish themselves in their tissue of origin.
Grosschedl and colleagues identify a role for the transcription factor EBF1 in bone marrow stromal cells that is required to maintain the niche to support hematopoietic stem cells and hematopoiesis.
Identifying selective tumor-associated molecules that can act as targets for T cells is a major goal of immunotherapy. Sewell and colleagues demonstrate that the nonclassical MHC molecule MR1 is expressed on a wide variety of cancer types and can be targeted by conventional T cells.
A subset of HIV-infected individuals can develop broadly neutralizing antibodies. Boyd and colleagues studied such HIV-infected individuals and found significant perturbations in their antibody repertoires, including increased frequencies of B cells expressing antibodies with features associated with autoreactivity.
Kohlmeier and colleagues showed that the airway environment drove transcriptional and epigenetic changes that regulated the cytolytic functions of airway TRM cells and promoted their apoptosis due to amino acid starvation and activation of the integrated stress response.
Hidalgo and colleagues describe a cell-intrinsic program that induces changes in the proteome, granule content and NET-forming capacity of neutrophils and is driven by the chemokine receptor CXCR2 and regulators of the circadian clock.
The protein STING has an essential function in intracellular DNA sensing, but how it is regulated under steady state is unclear. Yan and colleagues demonstrate that the protein TOLLIP stabilizes steady-state STING and facilitates its signaling.
Respiratory infections occur throughout life but how this shapes the lung immune system through time is unclear. Wack and colleagues show that a previous influenza infection recruits monocytes to the lung, which then assume an alveolar macrophage-like phenotype and mediate long-term antibacterial protection.
T cell homeostasis requires integration of signals from antigen and cytokine receptors. Gascoigne and colleagues demonstrate that the protein Themis supports signals from low-affinity TCR ligands to maintain normal CD8+ cell function.