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Visualization of IL-22-expressing Lymphocytes Using Reporter Mice

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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.

|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.

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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.