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Interleukin 20: discovery, receptor identification, and role in epidermal function
H Blumberg1, D Conklin, W F Xu
1Department of Genetics, ZymoGenetics, Inc., 1201 Eastlake Avenue E, Seattle, WA 98102, USA.
Cell
|February 13, 2001
Summary
Interleukin 20 (IL-20), a novel cytokine, was identified using bioinformatics. Its overexpression in mice caused skin abnormalities, and it plays a role in epidermal function and psoriasis.
Area of Science:
- Immunology
- Dermatology
- Bioinformatics
Background:
- Interleukin 10 (IL-10) is a key immunoregulatory cytokine.
- The IL-10 family of cytokines plays critical roles in immune responses and inflammation.
- Novel cytokines and their functions in skin biology remain an area of active research.
Purpose of the Study:
- To identify and characterize novel cytokines within the IL-10 family.
- To investigate the biological function of the newly identified cytokine, IL-20.
- To explore the role of IL-20 in skin homeostasis and disease, particularly psoriasis.
Main Methods:
- A structural, profile-based bioinformatics algorithm was employed for novel cytokine identification.
- Chromosomal localization was used to identify the IL-10 cytokine family cluster.
- Transgenic mouse models with IL-20 overexpression were generated to study in vivo effects.
- Recombinant IL-20 protein was used to assess signal transduction in keratinocyte cell lines.
- Identification of the IL-20 receptor as a heterodimer of orphan class II cytokine receptor subunits.
Main Results:
- A novel cytokine, interleukin 20 (IL-20), was identified as an IL-10 homolog.
- IL-20 overexpression in transgenic mice resulted in neonatal lethality and aberrant skin differentiation.
- Recombinant IL-20 activated STAT3 signaling in keratinocytes, indicating direct ligand action.
- The IL-20 receptor, composed of two orphan class II cytokine receptor subunits, was identified.
- Both IL-20 receptor subunits were expressed in skin and significantly upregulated in psoriatic lesions.
Conclusions:
- Interleukin 20 (IL-20) is a novel cytokine with a significant role in epidermal function.
- IL-20 signaling, mediated through its specific receptor, impacts keratinocyte differentiation.
- The upregulation of IL-20 and its receptor in psoriatic skin suggests involvement in the pathogenesis of psoriasis.
- Bioinformatics approaches are powerful tools for discovering novel cytokines and understanding their biological relevance.
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