B. Homey et al., Up-regulation of macrophage inflammatory protein-3 alpha/CCL20 and CC chemokine receptor 6 in psoriasis, J IMMUNOL, 164(12), 2000, pp. 6621-6632
Autoimmunity plays a key role in the immunopathogenesis of psoriasis; howev
er, little is known about the recruitment of pathogenic cells to skin lesio
ns. We report here that the CC chemokine, macrophage inflammatory protein-3
alpha, recently renamed CCL20, and its receptor CCR6 are markedly up-regul
ated in psoriasis, CCL20-expressing keratinocytes colocalize viith skin-inf
iltrating T cells in lesional psoriatic skin. PBMCs derived from psoriatic
patients show significantly increased CCR6 mRNA levels. Moreover, skin-homi
ng 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(+) me
mory 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 respon
ded to lower concentrations of chemokine and showed higher chemotactic resp
onses. Using ELISA as well as real-time quantitative PCR, we show that cult
ured primary keratinocytes, dermal fibroblasts, and dermal microvascular en
dothelial and dendritic tells are major sources of CCL20, and that the expr
ession of this chemokine can be induced by proinflammatory mediators such a
s TNF-alpha/IL-1 beta, CD40 ligand, IFN-gamma, or IL-17, Taken together, th
ese findings strongly suggest that CCL20/CCR6 may play a role in the recrui
tment of T cells to lesional psoriatic skin.