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Terrando and colleagues review key mechanisms related to postoperative inflammation and the implications for developing perioperative neurocognitive disorders, with a focus on neuroinflammation and key cellular targets affected by surgical trauma.
Exploring transcriptional heterogeneity of cKit+Sca1+ HSPCs using single cell RNA-sequencing, Naik and colleagues identify a population termed ‘lymphoid primed progenitors’ as the earliest stage of lymphoid lineage commitment, marked by downregulation of the stem/myeloid transcription factor Dach1.
Exposure to environmental pollutants can lead to immune system dysfunction with severe pathological consequences. Yamamoto and colleagues review the impact of pollutants on immune function and describe potential means to ameliorate these effects.
The identity of stem-cell memory progenitor cells has been unclear. Lugli and colleagues use high-dimensional approaches to identify two new progenitor populations of human T cells—one giving rise to a functional lineage, the other to an exhausted-like one.
CD4+ T cells are critical for effective responses to infection with the malaria parasite. Haque and colleagues use single-cell RNA sequencing and computational modeling to track T cell memory development during experimental Plasmodium infection of mice.
Sanz and colleagues examine B cell subsets in a cohort of patients with COVID-19. Severely ill patients have higher frequencies of activated extrafollicular T-bet+ B cells that form antibody-secreting cells, the majority of which express germline sequences and are reminiscent of antibody responses observed in patients with systemic lupus erythematosus during flares.
Sepsis is a biphasic disease characterized by an initial inflammatory phase, followed by a prolonged immunosuppression phase. Puthalakath and colleagues utilize a CRISPR-mediated mutagenesis screen to identify TREML4 as a regulator of sepsis-induced immunosuppression.
Humans with inherited defects in DOCK8 expression are prone to allergic, type 2 CD4+ T cell responses. Mandl and colleagues reveal an important role for cell death in driving such type 2 signals during infection.
Ho and colleagues report that mitochondrial dysfunction and impaired mitophagy triggered by the tumor microenvironment lead to subsequent epigenetic changes and cause permanent T cell exhaustion and dysfunction.
The pathways controlling T follicular helper (TFH) cell development are only partially understood. Allen and colleagues demonstrate the importance of the T cell receptor, with low tonic signaling promoting TFH cell development and high tonic signaling opposing it.
Treg cells are essential for immune homeostasis, but the transcription factors controlling their cellular identity are incompletely understood. Schumann and colleagues use pooled and arrayed CRISPR screens and scRNA-seq to describe key gene networks in human Treg cells.
Luster and colleagues show that Treg cells that reside in lung mucosa can respond to IL-33 upon allergen exposure and suppress innate cell responses. IL-33-activated ST2+ Treg cells secrete IL-35, which suppresses IL-17 production by γδ T cells and lessens eosinophil recruitment into the lung.
BATF3 is a member of the AP-1 transcription factor family. Kastenmüller and colleagues show that BATF3 is needed to promote memory CD8+ T cell responses. Activated CD8+ T cells transiently upregulate BATF3, which in turn suppresses expression of proapoptotic BIM to promote cell survival.
Phagocytes can acquire lipids and this modulates their function in a variety of disease states, such as atherosclerosis. Ren and colleagues demonstrate that neutrophils accumulate lipids and deliver them to tumor cells, which supports their proliferation, survival and metastasis.
Dysregulation of lung Treg cell function contributes to asthma development. Chatila and colleagues find that allergens upregulate Notch4–Hippo–Wnt signaling in Treg cells, triggering their release of GDF15 growth factor, which drives type 2 innate lymphoid cell activity and asthma.
IL-17a is an evolutionarily conserved cytokine with behavior-modulating roles in the central nervous system. Kipnis and colleagues characterize a population of meningeal γδ17 T cells that use IL-17a to elicit anxiety-like behavior through cortical glutamatergic neurons.
The adhesion receptor CD2 plays an important role in the full activation of T cells. Dustin and colleagues show that CD2 occupies a region in the periphery of the immunological synapse where it amplifies cognate antigen signals, whereas the presence of PD-1 disrupts this effect.
Questions have arisen as to whether patients with severe COVID-19 disease can generate a T cell response against SARS-CoV-2. Tao Dong and colleagues report that convalescent patients with COVID-19 harbor functional memory CD4+ and CD8+ T cells that recognize multiple epitopes that span the viral proteome. CD4+ T cells predominated the memory response in patients with severe disease, whereas higher proportions of CD8+ T cells were found in patients with mild disease.
Antigen-activated B cells are short lived in the absence of a second signal provided by CD4+ T cells or cytokines. Zikherman and colleagues report that the NR4A family of nuclear receptors (NUR77 and NOR-1) are responsible for enforcing this ‘tolerance’ to self-antigen (signal 1 only) and explain, in part, why B cells are dependent upon a second signal.
B cell development and selection occur in the often hypoxic environment of the bone marrow. Burrows and colleagues demonstrate that dynamic regulation of B cell–intrinsic hypoxia-inducible factor-1α is essential for normal B cell development and function.
Checkpoint blockade is effective in only a subset of patients; therefore, biomarkers that can predict efficacy would be clinically highly valuable. Nishkawa and colleagues develop a biomarker based on PD-1 positivity of effector and regulatory T cells in the tumor microenvironment that accurately predicts the effectiveness of checkpoint blockade in patients.
NKG7 is a molecule well associated with NK cells but of unknown function. Engwerda and colleagues demonstrate that NKG7 is also associated with TH1 cells and is essential for type I and cytotoxic responses.
Takayanagi and colleagues show that thymic medullary fibroblasts can contribute to central tolerance mechanisms by expressing cell-type-specific antigens distinct from those expressed by medullary thymic epithelial cells.
Diamond and colleagues generate a K18-hACE2 model of SARS-CoV-2 infection that shares many features of severe COVID-19 infection and can be used to define the basis of lung disease and test immune and antiviral-based countermeasures.
The developmental timing for exhaustion is still obscure. Kallies and colleagues demonstrate that CD8+ T cell ‘exhaustion’ actually begins in the less-differentiated TCF1+ ‘precursor’ T cell pool during chronic viral infections.
The angiocrine Rspondin3 is produced by endothelial cells (ECs) and controls growth and development. Malik and colleagues show that lung ECs produce Rspondin3 following injury and specifically direct interstitial macrophages into an anti-inflammatory and wound-healing program.
Pancreatic cancer has one of the worst survival outcomes of all cancers. Leinwand and Miller review the immunological landscape of pancreatic cancer, immune evasion mechanisms and the impact of the microbiota.
Accurate serology testing is urgently needed to help diagnose SARS-CoV-2 infection. Here Valkenburg and colleagues use a luciferase immunoprecipitation system to assess the antibody responses to 15 different SARS-CoV-2 antigens in patients with COVID-19 and find ORF8 and ORF3b antibodies, taken together as a cluster of points, identified 96.5% of COVID-19 samples at early and late time points of disease with 99.5% specificity
Severe COVID-19 is characterized—among other things—by a hyperinflammatory state. Wang and colleagues describe the single-cell transcriptional landscape of moderate, severe and convalescent cases of patients with COVID-19.
Obesity is often accompanied by chronic inflammation. Li and colleagues show that, in mice fed high-fat diets, IL-1 signaling in adipocytes induces an unconventional IRAK2 translocation to mitochondria and suppresses respiratory super-complex formation to alter mitochondrial function, and exacerbates obesity.
Autophagy controls cellular homeostasis and influences immune responses. Galluzzi and colleagues show that tumor cell autophagy opposes inflammatory cell death following radiation therapy and can be inhibited to enhance antitumor responses.
The CTLA-4–Ig fusion protein (abatacept) can have beneficial effects in autoimmune disease. Walker and colleagues show in mouse and human type 1 diabetes that abatacept targets pathogenic follicular helper T cells, and the frequencies of these cells at baseline can be used to stratify treatment responses in patients.
Koliaraki, Prados, Armaka & Kollias review the roles of fibroblastic mesenchymal cells in tissue homeostasis and immunopathologic diseases, including chronic inflammatory disease, tissue fibrosis and cancer.
Pathological group 2 innate lymphoid cells (ILC2s) have mainly been implicated in allergy. Halim and colleagues demonstrate that ILC2s orchestrate a prometastatic pathway via the recruitment of eosinophils that suppress NK cell function.
Banchereau and colleagues provide a resource dataset that examines disease-related transcriptional profiles of peripheral whole-blood cells from adolescent patients with SLE by single-cell RNA-seq analysis.
The epigenetic landscape of human αβ and γδT cell development has remained unexplored thus far. Taghon and colleagues provide a resource of RNA-seq and ATAC–seq profiles examining human thymocyte development.
Luo and colleagues use single-cell RNA sequencing to provide a comprehensive transcriptional landscape of neutrophil maturation, function and fate decision in their steady state and during bacterial infection.
Verykokakis and colleagues show that the transcription factor BCL-6 is highly expressed in stage 0 NKT and is absolutely required for innate T cell lineage development. BCL-6 acts to modify the chromatin landscape and is needed to promote the ST0–ST1 transition and PLZF expression.