RGD Reference Report - Up-regulation of macrophage inflammatory protein-3 alpha/CCL20 and CC chemokine receptor 6 in psoriasis. - Rat Genome Database

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Up-regulation of macrophage inflammatory protein-3 alpha/CCL20 and CC chemokine receptor 6 in psoriasis.

Authors: Homey, B  Dieu-Nosjean, MC  Wiesenborn, A  Massacrier, C  Pin, JJ  Oldham, E  Catron, D  Buchanan, ME  Muller, A  DeWaal Malefyt, R  Deng, G  Orozco, R  Ruzicka, T  Lehmann, P  Lebecque, S  Caux, C  Zlotnik, A 
Citation: Homey B, etal., J Immunol. 2000 Jun 15;164(12):6621-32.
RGD ID: 7483581
Pubmed: PMID:10843722   (View Abstract at PubMed)

Autoimmunity plays a key role in the immunopathogenesis of psoriasis; however, little is known about the recruitment of pathogenic cells to skin lesions. We report here that the CC chemokine, macrophage inflammatory protein-3 alpha, recently renamed CCL20, and its receptor CCR6 are markedly up-regulated in psoriasis. CCL20-expressing keratinocytes colocalize with skin-infiltrating T cells in lesional psoriatic skin. PBMCs derived from psoriatic patients show significantly increased CCR6 mRNA levels. Moreover, skin-homing CLA+ memory T cells express high levels of surface CCR6. Furthermore, the expression of CCR6 mRNA is 100- to 1000-fold higher on sorted CLA+ memory T cells than other chemokine receptors, including CXCR1, CXCR2, CXCR3, CCR2, CCR3, and CCR5. In vitro, CCL20 attracted skin-homing CLA+ T cells of both normal and psoriatic donors; however, psoriatic lymphocytes responded to lower concentrations of chemokine and showed higher chemotactic responses. Using ELISA as well as real-time quantitative PCR, we show that cultured primary keratinocytes, dermal fibroblasts, and dermal microvascular endothelial and dendritic cells are major sources of CCL20, and that the expression of this chemokine can be induced by proinflammatory mediators such as TNF-alpha/IL-1 beta, CD40 ligand, IFN-gamma, or IL-17. Taken together, these findings strongly suggest that CCL20/CCR6 may play a role in the recruitment of T cells to lesional psoriatic skin.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
psoriasis  IEP 7483581; 7483581mRNA:increased expression:skinRGD 
psoriasis  ISOCCL20 (Homo sapiens)7483581; 7483581mRNA:increased expression:skinRGD 
psoriasis  ISOCCR6 (Homo sapiens)7483581; 7483581mRNA:increased expression:skinRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl20  (C-C motif chemokine ligand 20)
Ccr6  (C-C motif chemokine receptor 6)

Genes (Mus musculus)
Ccl20  (C-C motif chemokine ligand 20)
Ccr6  (C-C motif chemokine receptor 6)

Genes (Homo sapiens)
CCL20  (C-C motif chemokine ligand 20)
CCR6  (C-C motif chemokine receptor 6)


Additional Information