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Lymphocyte Isolation from Human Skin for Phenotypic Analysis and Ex Vivo Cell Culture
Published on: April 8, 2016
The type I interferon system is locally activated in psoriatic lesions
Abstract:
The expression of mRNAs encoding interferons (IFNs) and IFN-inducible proteins has been studied in psoriatic lesions and in noninvolved skin. The specific mRNAs have been detected by in situ hybridization using antisense RNAs. Signals for the expression of IFN-gamma mRNA have been found exclusively in cells of psoriatic lesions, and most likely represent a subpopulation of infiltrating leukocytes. Weak signals of IFN-alpha mRNA have been detected throughout the hyperkeratotic epidermis, although specific signals for IFN-beta mRNA expression were not detectable. The expression of two IFN-alpha-inducible gene products, namely the MxA protein and the 2'-5' oligoadenylate (2-5A) synthetase, have been studied as markers for the local activation of the IFN-alpha system. Expression of MxA mRNA and protein was observed in psoriatic keratinocytes, but not in normal appearing keratinocytes adjacent to the lesions. Similarly, 2-5A synthetase expression was markedly elevated in psoriatic keratinocytes. The results of the present study indicate that the IFN-alpha system is selectively activated in psoriatic lesions, although it remains silent in noninvolved skin. The implications of this finding are discussed within the boundaries of current understanding of the cytokine network.
Insights
The interferon (IFN) system is activated in psoriatic lesions, with IFN-gamma mRNA found in infiltrating leukocytes and IFN-alpha-inducible proteins in keratinocytes. This suggests a localized immune response specific to psoriasis.
Area of Science:
- Immunology
- Dermatology
- Molecular Biology
Background:
- Psoriasis is a chronic inflammatory skin disease.
- The role of interferons (IFNs) in psoriasis pathogenesis is not fully understood.
- Investigating the local expression of IFNs and IFN-inducible genes can elucidate disease mechanisms.
Purpose of the Study:
- To investigate the expression patterns of interferon-gamma (IFN-gamma) mRNA, interferon-alpha (IFN-alpha) mRNA, and IFN-alpha-inducible genes in psoriatic lesions and noninvolved skin.
- To determine if the interferon-alpha system is locally activated in psoriatic skin.
Main Methods:
- In situ hybridization was used to detect specific mRNA expression.
- Antisense RNAs were employed as probes for mRNA detection.
- Expression of MxA protein and 2'-5' oligoadenylate (2-5A) synthetase was analyzed as markers for IFN-alpha system activation.
Main Results:
- IFN-gamma mRNA was exclusively detected in psoriatic lesions, likely within infiltrating leukocytes.
- Weak signals for IFN-alpha mRNA were found in the hyperkeratotic epidermis of psoriatic lesions.
- Expression of MxA and 2-5A synthetase was significantly elevated in psoriatic keratinocytes compared to normal keratinocytes.
Conclusions:
- The interferon-alpha system is selectively activated within psoriatic skin lesions.
- This localized activation suggests a role for the IFN-alpha pathway in psoriasis pathogenesis.
- The findings contribute to understanding the cytokine network in inflammatory skin diseases.
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