Adaptive behaviors in hematopoietic cells can promote homeostasis and enhance immune responses to pathogens, but they can also perpetuate the chronicity of inflammatory or metabolic disorders.
Nature Immunology presents three Reviews that discuss the metabolic and molecular mechanisms that allow immune cells and hematopoietic progenitor cells to adapt to diverse environments or pathophysiological conditions, and how these mechanism can be advantageous or can perpetuate the chronicity of various disorders.
Reviews and Perspectives
In this Review, Natoli and Ostuni discuss the mechanisms of adaptation and memory in immunity, with the aim of providing basic concepts that rationalize the properties and molecular bases of these essential processes.
In this Review, Pearce and colleagues discuss the metabolic adaptation of immune cells to various tissues and how functional adaptation compared with maladaptation within the niche can affect tissue homeostasis.
Hematopoietic progenitor cells as integrative hubs for adaptation to and fine-tuning of inflammation
In this Review, Chavakis and colleagues discuss the mechanisms that govern the adaptation of hematopoietic progenitor cells to inflammation and its effects on the pathogenesis of human disease.
From the archive
Bhlhe40 mediates tissue-specific control of macrophage proliferation in homeostasis and type 2 immunity
Edelson and colleagues show that the transcription factor Bhlhe40 is required in a cell-intrinsic manner for the self-renewal and maintenance of large peritoneal macrophages, but not that of other tissue-resident macrophages.
SUCNR1 controls an anti-inflammatory program in macrophages to regulate the metabolic response to obesity
Succinate is a signaling metabolite sensed extracellularly by SUNCR1. Fernandez-Veledo and colleagues show that activation of SUCNR1 promotes an anti-inflammatory phenotype in adipose-tissue macrophages in lean mice and people.
IL-17 metabolically reprograms activated fibroblastic reticular cells for proliferation and survival
Fibroblastic reticular cells support lymph-node function and adaptive immunity. McGeachy and colleagues show that the cytokine IL-17 is needed to trigger metabolic changes required for the proliferation and survival of these cells in reactive lymph nodes.
Regulatory T cells obstruct effective anti-cancer immune responses. Vignali and colleagues demonstrate that IL-10 production and IL-35 production by tumor-infiltrating regulatory T cells mediate differential and non-redundant suppressive effects on tumor-reactive cytotoxic T cells.
The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation
Control of macrophage activation in the lungs is essential for the prevention of tissue damage. MacDonald and colleagues show that alveolar macrophages have impaired glycolysis and are hyporesponsive during type 2 inflammation in a manner controlled by the lung environment.
Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration
Muscle damage elicits a sterile immune response that facilitates complete regeneration. Nagy and colleagues map the mediator lipidome during the transition from inflammation to resolution in skeletal muscle injury.
Neutrophils rapidly respond to bacterial and fungal infections but can cause substantial collateral tissue damage if not restrained. Rosenbauer and colleagues show that the transcription factor PU.1 serves a cell-intrinsic role to prevent over-exuberant neutrophil responses to fungal infection.
The skin and intestine are unique environments at the front line of the immune system. Powrie and colleagues review the distinctive adaptations acquired by regulatory T cells at these barrier surfaces.
The role of IFN-λ in adaptive immunity is not well characterized. Staeheli and colleagues show that in the lungs, IFN-λ elicits production of the cytokine TSLP from M cells and that this in turn is essential for effective adaptive immunity and control of infection with influenza virus.
Inflammatory macrophage dependence on NAD+ salvage is a consequence of reactive oxygen species–mediated DNA damage
Macrophages can shift their cellular metabolism in response to tissue cues and infection. Pearce and colleagues show that lipopolysaccharide-activated ‘inflammatory’ macrophages become depleted of NAD+ pools and require the salvage-pathway enzyme NAMPT to sustain cellular redox balance.
Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade
Exhausted cytotoxic T lymphocytes (CTLs) express the receptor PD-1 as a key signature. Haining and colleagues show that there are different ‘depths’ of exhaustion with a subset of exhausted CTLs that retain polyfunctionality and are responsive to PD-1 blockade.
Epelman and colleagues use fate mapping and single-cell transcriptomics to describe the dynamics of resident and recruited cardiac macrophages during ischemic injury.
DEL-1 protein interferes with leukocyte adhesion to prevent inflammation. Chavakis and colleagues now show that DEL-1 contributes to tissue resolution after inflammation by promoting macrophage-mediated efferocytosis and M2-like pro-resolving activities.
Macrophages alter their metabolism in response to infection. The authors show that resting macrophages generate nicotinamide adenine dinucleotide via de novo synthesis, but activated and aged cells suppress the rate-limiting enzyme quinolinate phosphoribosyltransferase to regulate mitochondrial and immunological functions.
Tissue-resident memory cells are functionally distinct from lymph node memory cells. Randall and colleagues show that lung infection establishes B cell memory in situ and confers superior responses following challenge infection, which will inform vaccine design for respiratory viruses.