Increased CCL27-CCR10 expression in allergic contact dermatitis: implications for local skin memory.
Allergic contact dermatitis (ACD) is a T-cell-mediated disease in which expression of a distinct repertoire of chemokines results in the recruitment of effector T cells into the skin. While it is becoming clear which chemokines and receptors determine the development of ACD, the mechanisms involved in the retention of T cells in the skin after resolution of inflammation are still unknown. Unravelling these mechanisms will help us to understand local skin memory as observed in retest reactivity and flare-up reactions. This study was designed to evaluate the role of chemokine-chemokine receptor interactions in local T-cell retention. The results show that expression of the CCR10 targeting ligand CCL27 is not only increased during inflammation, but also remains increased several weeks after clinical responsiveness to patch testing. In parallel with increased CCL27 expression, an increased number of infiltrating cells could still be detected in skin that, clinically, had returned to normal 21 days after patch testing. These persisting cells were characterized as CD4+ cells expressing CCR10, while no CD8+ CCR10+ cells could be detected. The presence of these cells is most likely an allergen-mediated effect, as increased levels of CCL27 and CCR10 could not be detected 21 days after initiating an irritant contact dermatitis reaction. In contrast to CCL27, increased expression of CXCL9, CXCL10, and CXCL11 could only be observed during the clinically inflammatory phase of ACD. In conclusion, local CCL27-mediated retention of CCR10+ CD4+ T cells in sites previously challenged by ACD could be responsible for phenomena such as local skin memory observed in retest reactions and flare-up reactions in which the presence of persisting T cells results in an accelerated inflammatory response upon renewed allergen challenge.
Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands.
Heleen
H
Moed
Dick M
DM
Boorsma
Cornelis P
CP
Tensen
Jacoba
J
Flier
Maureen J
MJ
Jonker
Tom J
TJ
Stoof
B Mary E
BM
von Blomberg
Derk P
DP
Bruynzeel
Rik J
RJ
Scheper
Thomas
T
Rustemeyer
Susan
S
Gibbs
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054425:Chemokine CCL27; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000473:pathology; D017453:Dermatitis, Irritant / Q000276:immunology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D007156:Immunologic Memory; D017403:In Situ Hybridization; D010328:Patch Tests; D012333:RNA, Messenger / Q000235:genetics; D054447:Receptors, CCR10; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000276:immunology*; D013997:Time Factors
C492276:CCL27 protein, human; C515706:CCR10 protein, human; D054425:Chemokine CCL27; D019742:Chemokines, CC; D012333:RNA, Messenger; D054447:Receptors, CCR10; D019707:Receptors, Chemokine