Dendritic cells (DCs) are professional antigen-presenting cells, orchestrating innate and adaptive immunity during infections, autoimmune diseases, and malignancies. Since the discovery of DCs almost 50 years ago, our understanding of their biology in humans has increased substantially. Here, we review both antitumor and tolerogenic DC responses in cancer and discuss lineage-specific contributions by their functionally specialized subsets, including the conventional DC (cDC) subsets cDC1 and cDC2, the newly described DC3, and the plasmacytoid DCs (pDCs), focusing on the human setting. In addition, we review the lineage-unrestricted “mature DCs enriched in immunoregulatory molecules” (mregDC) state recently described across different human tumors.

Human uterine NK cells continuously differentiate in response to the monthly regeneration of the endometrium and during pregnancy.

Significance: While broad efforts toward getting an overview of immune cell and soluble factor alterations in COVID-19 are under way, a deep and comprehensive understanding of the mononuclear phagocyte system, including circulating progenitors, is still largely lacking. This study provides a reference for the mononuclear phagocyte response to SARS-CoV-2 infection and unravels mononuclear phagocyte dysregulations associated with severe COVID-19.

Neutrophils are the most abundant leucocytes in human blood, promptly recruited to the site of tissue injury, where they orchestrate inflammation and tissue repair. The multifaceted functions of neutrophils have been more appreciated during the recent decade, and these cells are now recognized as sophisticated and essential players in infection, cancer and chronic inflammatory diseases. Consequently, our understanding of the role of neutrophils in inflammatory bowel disease (IBD), their immune responses and their ability to shape adaptive immunity in the gut have been recognized. Here, current knowledge on neutrophil responses in IBD and their capacity to influence T cells are summarized with an emphasis on the role of these cells in human disease.

Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut injury model and human ex vivo transcriptomic, protein and spatial analyses, we report that PDGFRA⁺CD142^−/low fibroblasts and monocytes/macrophages co-localize in the intestine. In primary human fibroblast-monocyte co-cultures, intestinal PDGFRA⁺CD142^−/low fibroblasts foster monocyte transition to CCR2⁺CD206⁺ macrophages through granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte-derived CCR2⁺CD206⁺ cells from co-cultures have a phenotype similar to intestinal CCR2⁺CD206⁺ macrophages from newly diagnosed pediatric IBD patients, with high levels of PD-L1 and low levels of GM-CSF receptor. The study describes subset-specific changes in stromal responses to inflammation and suggests that the intestinal stroma guides intestinal macrophage differentiation.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm caused by aberrant activation of the mitogen-activated protein kinase (MAPK) pathway. Circulating myeloid cells from patients often carry disease-associated mutations and can be differentiated into langerinhigh LCH-like cells in vitro, but their detailed immune-phenotypic and molecular profiles are lacking and could shed key insights into disease biology. Here we recruited 217 pediatric LCH patients and took blood and tissue samples for BRAFV600E analysis. Immune-phenotyping of the circulating Lin−HLA-DR+ immune population in 49 of these patients revealed that decreased frequency of plasmacytoid dendritic cells was significantly linked to disease severity. By single-cell RNA sequencing of samples from 14 patients, we identified key changes in expression of RAS-MAPK-extracellular signal-regulated kinase (ERK) signaling-related genes and transcription factors in distinct members of the mononuclear phagocyte system in the presence of BRAFV600E. Moreover, treatment of patients with the BRAF inhibitor dabrafenib resulted in MAPK cascade inhibition, inflammation prevention, and regulation of cellular metabolism within mononuclear phagocytes. Finally, we also observed elevated expression of RAS-MAPK-ERK signaling-related genes in a CD207+CD1a+ cell subcluster in skin. Taken together, our data extend the molecular understanding of LCH biology at single-cell resolution, which might contribute to improvement of clinical diagnostics and therapeutics, and aid in the development of personalized medicine approaches.