Chemerin

Chemerin is a leukocyte-attractant, adipokine and antimicrobial protein. The adipokine chemerin acts as a ligand for the G-protein-coupled receptor CMKLR1 and also binds to two atypical heptahelical receptors, CCRL2 and GPR1. The coding gene is the RARRES2 gene.

Chemerin, CMKLR1, CCRL2 and GPR1 are expressed in the epidermis of humans, suggesting that this tissue may be both a source and a target for chemerin-mediated effects. The major cellular receptors of chemerin, chemokine-like receptor 1 (CMKLR1), G-protein-coupled receptor 1 (GPR1) and C-C chemokine receptor-like 2 (CCRL2), are expressed in most normal and tumor tissues (Treeck O et al. 2019).

In human skin cultures, chemerin is significantly downregulated by IL-17 and IL-22, important cytokines involved in psoriasis, while it is upregulated by the acute-phase cytokines oncostatin M (seeoncostatin M receptor below) and IL-1β.

Although chemerin was originally identified as a gene highly expressed in healthy skin keratinocytes that is downregulated in psoriasis, the regulation of chemerin and its receptors in the skin by specific cytokines and microbial factors is largely unknown.

Chemerin is the only inflammatory chemotactic factor that acts directly on pDC(plasmacytoid dendritic cells) in human blood in vitro. Prepsoriatic skin adjacent to active lesions and early lesions is characterized by a strong expression of chemerin in the dermis and by the presence of CD15⁽⁺) neutrophils and CD123⁽⁺)/BDCA-2(+)/ChemR23⁽⁺)-pDC. In contrast, skin from chronic plaques showed low chemerin expression, segregation of neutrophils into epidermal microabscesses and few pDC in the dermis. Chemerin expression was mainly localized in fibroblasts, mast cells and endothelial cells. These results support a role of the chemerin/ChemR23 axis in the early stages of psoriasis development (Albanesi C et al. 2009).

In addition, chemerin is required for maximal bactericidal effects in vivo in a skin infection model (Banas M et al. 2015).

1. Albanesi C et al. (2009) Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment. J Exp Med 206:249-258.
2. Banas M et al. (2015) The expression and regulation of chemerin in the epidermis. PLoS One 10:e0117830.
3. De Henau O et al. (2016) Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2. PLoS One 11:e0164179.
4. Pawlik KK et al.(2020) BIOMARKERS OF DISEASE ACTIVITY IN SYSTEMIC SCLEROSIS. Wiad Lek 73:2300-2305.
5. Sawicka K et al. (2019) Visfatin and chemerin levels correspond with inflammation and might reflect the bridge between metabolism, inflammation and fibrosis in patients with systemic sclerosis. Postepy Dermatol Alergol 36:551-565.
6. Treeck O et al (2019) Chemerin and Cancer. Int J Mol Sci 20:3750