Dendritic cells (DCs) are antigen-presenting cells controlling T cell activation. In humans, the diversity, ontogeny, and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88CD1cCD163 DCs (called DC3s) as immediate precursors of inflammatory CD88CD14CD1cCD163FcεRI DCs. DC3s develop via a specific pathway activated by GM-CSF, independent of cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors. Like classical DCs but unlike monocytes, DC3s drove activation of naive T cells. In vitro, DC3s displayed a distinctive ability to prime CD8 T cells expressing a tissue homing signature and the epithelial homing alpha-E integrin (CD103) through transforming growth factor β (TGF-β) signaling. In vivo, DC3s infiltrated luminal breast cancer primary tumors, and DC3 infiltration correlated positively with CD8CD103CD69 tissue-resident memory T cells. Together, these findings define DC3s as a lineage of inflammatory DCs endowed with a strong potential to regulate tumor immunity.
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http://dx.doi.org/10.1016/j.immuni.2020.06.002 | DOI Listing |
Unlabelled: Dendritic cells (DCs) are key regulators of adaptive immunity, guiding T helper (Th) cell differentiation through antigen presentation, co-stimulation, and cytokine production. However, in steady-state conditions, certain DC subsets, such as Langerhans cells (LCs), induce T follicular helper (Tfh) cells and B cell responses without inflammatory stimuli. Using multiple mouse models and systems, we investigated the mechanisms underlying steady-state LC-induced adaptive immune responses.
View Article and Find Full Text PDFHead and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. HPV-negative HNSCC, which arises in the upper airway mucosa, is particularly aggressive, with nearly half of patients succumbing to the disease within five years and limited response to immune checkpoint inhibitors compared to other cancers. There is a need to further explore the complex immune landscape in HPV-negative HNSCC to identify potential therapeutic targets.
View Article and Find Full Text PDFThis 30-color panel was developed to enable the enumeration and purification of distinct circulating immune cell subsets implicated in the pathogenesis of systemic autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc; scleroderma), Sjögren's disease (SjD), idiopathic inflammatory myopathy (IIM), and others. While designed for application to peripheral blood mononuclear cells, the inclusion of CD45 coupled with the ability to extract cellular autofluorescence spectral signatures enables the application of this panel to other tissue types. Of the 30 total markers, this panel employs 18 markers to profile T cell subsets consisting of different memory subsets and T helper polarities, > 10 markers to profile B cell subsets including double-negative B cells, and a total of 8 lineage markers to identify immune lineages including monocyte and natural killer cell subsets, conventional dendritic cells, plasmacytoid dendritic cells, and basophils.
View Article and Find Full Text PDFGamma oscillations are disrupted in various neurological disorders, including Alzheimer's disease (AD). In AD mouse models, non-invasive audiovisual stimulation (AuViS) at 40 Hz enhances gamma oscillations, clears amyloid-beta, and improves cognition. We investigated mechanisms of circuit remodeling underlying these restorative effects by leveraging the sensitivity of hippocampal neurogenesis to activity in middle-aged wild-type mice.
View Article and Find Full Text PDFBioact Mater
April 2025
School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, 214122, PR China.
Peptide vaccines based on tumor antigens face the challenges of rapid clearance of peptides, low immunogenicity, and immune suppressive tumor microenvironment. However, the traditional solution mainly uses exogenous substances as adjuvants or carriers to enhance innate immune responses, but excessive inflammation can damage adaptive immunity. In the current study, we propose a straightforward novel nanovaccine strategy by employing homologous human ferritin light chain for minimized innate immunity and dendritic cell (DC) targeting, the cationic KALA peptide for enhanced cellular uptake, and suppressor of cytokine signaling 1 (SOCS1) siRNA for modulating DC activity.
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