CC chemokine ligand 18, an atopic dermatitis-associated and dendritic cell-derived chemokine, is regulated by staphylococcal products and allergen exposure.
Atopic dermatitis is a chronic inflammatory skin disease with a steadily increasing prevalence. Exposure to allergens or bacterial superantigens triggers T and dendritic cell (DC) recruitment and induces atopic skin inflammation. In this study, we report that among all known chemokines CCL18/DC-CK1/PARC represents the most highly expressed ligand in atopic dermatitis. Moreover, CCL18 expression is associated with an atopic dermatitis phenotype when compared with other chronic inflammatory skin diseases. DCs either dispersed within the dermis or clustering at sites showing perivascular infiltrates are abundant sources of CCL18. In vitro, microbial products including LPS, peptidoglycan, and mannan, as well as the T cell-derived activation signal CD40L, induced CCL18 in monocytes. In contrast to monocytes, monocyte-derived, interstitial-type, and Langerhans-type DCs showed a constitutive and abundant expression of CCL18. In comparison to Langerhans cells, interstitial-type DCs produced higher constitutive levels of CCL18. In vivo, topical exposure to the relevant allergen or the superantigen staphylococcal enterotoxin B, resulted in a significant induction of CCL18 in atopic dermatitis patients. Furthermore, in nonatopic NiSO4-sensitized individuals, only relevant allergen but not irritant exposure resulted in the induction of CCL18. Taken together, findings of the present study demonstrate that CCL18 is associated with an atopy/allergy skin phenotype, and is expressed at the interface between the environment and the host by cells constantly screening foreign Ags. Its regulation by allergen exposure and microbial products suggests an important role for CCL18 in the initiation and amplification of atopic skin inflammation.
Pivarcsi
Andor
A
Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany.
Gombert
Michael
M
Dieu-Nosjean
Marie-Caroline
MC
Lauerma
Antti
A
Kubitza
Robert
R
Meller
Stephan
S
Rieker
Juliane
J
Muller
Anja
A
Da Cunha
Ludivine
L
Haahtela
Anna
A
Sonkoly
Eniko
E
Fridman
Wolf-Herman
WH
Alenius
Harri
H
Kemeny
Lajos
L
Ruzicka
Thomas
T
Zlotnik
Albert
A
Homey
Bernhard
B
D000485:Allergens / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D010641:Phenotype; D011565:Psoriasis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D012867:Skin / Q000098:blood supply / Q000276:immunology / Q000378:metabolism; D013210:Staphylococcus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology
D000485:Allergens; D000942:Antigens, Bacterial; C111792:CCL18 protein, human; D019742:Chemokines, CC; D004768:Enterotoxins; D018089:Superantigens; C031818:enterotoxin B, staphylococcal