PubMed · 1471777
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
H A Sampson. 1992. Atopic dermatitis.. https://pubmed.ncbi.nlm.nih.gov/1471777/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
BACKGROUND: Atopic dermatitis (AD), a common chronic inflammatory skin disease, has been extensively studied using single-cell genomics. However, keratinocytes, as key effector cells in AD, have underlying mechanisms remain incompletely understood and require further investigation. METHODS: We integrated single-cell transcriptomic data from skin tissues of healthy controls, chronic active AD patients, spontaneously healed AD (SHAD) patients, and an ovalbumin-induced AD mouse model. The study particularly emphasized the gene expression and cellular dynamics of keratinocytes across the different groups, as well as their interactions with immune cells. RESULTS: Compared to healthy controls, we observed significant changes in the keratinocyte transcriptome, cellular state, and keratinocyte-immune cell ligand-receptor interactions in AD skin, particularly the marked activation of genes involved in antigen processing and presentation. Interestingly, such gene activation was not observed in keratinocytes from the ovalbumin-induced AD mouse model, despite its phenotype closely resembling human AD. Furthermore, in SHAD, we identified a recovery of both the ligand-receptor interaction patterns and antigen processing and presentation genes, accompanied by a notable shift in the transcriptome. This involved a significant downregulation of genes related to cytoplasmic transcription and oxidative phosphorylation. Notably, this pattern was not observed in the self-healing mouse model following the removal of ovalbumin stimulation. CONCLUSION: Our results suggest that the persistent activation of antigen processing and presentation pathways in keratinocytes may be a key driver of chronic inflammation in AD. Therefore, redirecting anti-allergic therapeutic strategies from solely targeting immune cells to targeting of keratinocyte-mediated antigen presentation may offer a more effective approach. Furthermore, we raise concerns about the use of ovalbumin-induced mouse models to recapitulate human chronic AD, as the underlying mechanisms may differ significantly.
The extracellular matrix protein, Fn, has critical functions in cell attachment, migration, differentiation, and proliferation. We have previously shown that fibronectin (Fn) is abnormally expressed and potentiates entry into the cell cycle of basal keratinocytes in uninvolved psoriatic skin, in combination with T cell lymphokines. It is not known what type of Fn is present in psoriatic skin, however, and how this Fn may regulate signaling. Embryonic forms of cellular Fn containing extra domains, designated EDA and EDB, are generated by alternative splicing and are seen in proliferating, developing tissue and in wound healing. Because the EDA segment enhances the integrin binding sequence Arg, Gly, Asp (RGD), which, when present, has been shown to be critical in integrin-extracellular matrix signaling, we were particularly interested in determining whether or not EDA-containing Fn (EDA+Fn) represented the aberrantly expressed Fn in psoriasis. Increased EDA+ Fn protein was demonstrated by immunostaining at the dermal-epidermal junction in clinically uninvolved skin from six of six patients with psoriasis, but not in skin from control subjects. Using reverse transcription polymerase chain reaction an increased ratio of EDA+ Fn versus EDA- Fn mRNA was present in epidermal samples from psoriatic but not control individuals. Interestingly, the EDA+Fn in the psoriatic epidermis had the IIICS region spliced out (EDA+, FDB-, IIICS-, III9+), which was shared with normal epidermis (EDA-, EDB-, IIICS-, III9+). These results suggest a selective predominance of the EDA+ Fn isoform at the dermal-epidermal junction of psoriatic skin. The consistent aberrant localization of EDA+ Fn at the dermal-epidermal junction in uninvolved skin of psoriatics may confer the hyperresponsiveness of psoriatic uninvolved basal keratinocytes for rapid cellular proliferation in response to T cell signals. Key words: immunohistochemistry/integrin/keratinocyte/RT-PCR.
For the treatment of atopic dermatitis topical therapy prevails. The proper choice of the appropriate base is hereby decisive for an optimal topical therapy. It is governed by the clinical assessment of the state of the skin. Of particular importance is furthermore the persistent use of a basic treatment with ointments in order to restore skin fat and an active involvement of the patient in the choice for the appropriate preparation.