ArticleThe Journal of allergy and clinical immunology2017
Human skin dendritic cell fate is differentially regulated by the monocyte identity factor Kruppel-like factor 4 during steady state and inflammation.
Article in The Journal of allergy and clinical immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- BRAFV600E induces key features of LCH in iPSCs with cell type-specific phenotypes and drug responses.Blood · 2025Article
- Immunological control of skin development: from homeostasis to developmental pathologies.Frontiers in immunology · 2025Review
- Krüppel-like factor 4 control of immune cell function.Frontiers in immunology · 2025Review
- The role of KLF4 in phagocyte activation during infectious diseases.Frontiers in immunology · 2025Review
- Monocyte-derived Langerhans cells express Delta-like 4 induced by peptidoglycan and interleukin-4 mediated suppression.Frontiers in immunology · 2025Article
- Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity.Science immunology · 2024Article
- Targeting DNA methylation and demethylation in diabetic foot ulcers.Journal of advanced research · 2023Review
- BRAFLeukemia · 2023Article
- Microenvironmental and cell intrinsic factors governing human cDC2 differentiation and monocyte reprogramming.Frontiers in immunology · 2023Article
- Notch-dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology.Science immunology · 2022Article
- Loss of T cell tolerance in the skin following immunopathology is linked to failed restoration of the dermal niche by recruited macrophages.Cell reports · 2022Article
- Pathological and protective roles of dendritic cells inFrontiers in cellular and infection microbiology · 2022Review
- The developing immune network in human prenatal skin.Immunology · 2020Review
- Human dendritic cell subsets: an update.Immunology · 2018Review
- Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation.The Journal of experimental medicine · 2018Article
- Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults.Blood · 2017Article
- Aging and the Krüppel-like factors.Trends in cell & molecular biology · 2017Article
- GM-CSF Monocyte-Derived Cells and Langerhans Cells As Part of the Dendritic Cell Family.Frontiers in immunology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundLangerhans cell (LC) networks play key roles in immunity and tolerance at body surfaces. LCs are established prenatally and can be replenished from blood monocytes. Unlike skin-resident dermal DCs (dDCs)/interstitial-type DCs and inflammatory dendritic epidermal cells appearing in dermatitis/eczema lesions, LCs lack key monocyte-affiliated markers. Inversely, LCs express various epithelial genes critical for their long-term peripheral tissue residency.
objectiveDendritic cells (DCs) are functionally involved in inflammatory diseases; however, the mechanisms remained poorly understood.
methodsIn vitro differentiation models of human DCs, gene profiling, gene transduction, and immunohistology were used to identify molecules involved in DC subset specification.
resultsHere we identified the monocyte/macrophage lineage identity transcription factor Kruppel-like factor 4 (KLF4) to be inhibited during LC differentiation from human blood monocytes. Conversely, KLF4 is maintained or induced during dermal DC and monocyte-derived dendritic cell/inflammatory dendritic epidermal cell differentiation. We showed that in monocytic cells KLF4 has to be repressed to allow their differentiation into LCs. Moreover, respective KLF4 levels in DC subsets positively correlate with proinflammatory characteristics. We identified epithelial Notch signaling to repress KLF4 in monocytes undergoing LC commitment. Loss of KLF4 in monocytes transcriptionally derepresses Runt-related transcription factor 3 in response to TGF-β1, thereby allowing LC differentiation marked by a low cytokine expression profile.
conclusionMonocyte differentiation into LCs depends on activation of Notch signaling and the concomitant loss of KLF4.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.