Thymus- and activation-regulated chemokine (TARC/CCL17) induces a Th2-dominated inflammatory reaction on intradermal injection in mice.
TARC/CCL17 (thymus- and activation-regulated chemokine) is a CC chemokine, which binds to the CC chemokine receptor-4 (CCR4) known to be distinctively expressed on Th2 lymphocytes. In atopic dermatitis (AD), the skin is invaded by Th2 lymphocytes in the acute phase. TARC/CCL17 is produced by the keratinocytes in AD lesions, and CCR4 is overexpressed on CLA+ (cutaneous lymphocyte-associated antigen) lymphocytes in the skin and blood. We, therefore, hypothesized that TARC/CCL17 is pivotal in mediating a Th2-dominated inflammation in the skin. To examine this, we injected BALB/c mice with murine TARC/CCL17 in concentrations ranging from 0.1 microg/ml to 10 microg/ml and examined the skin after 48 h. This revealed that TARC/CCL17 induces lymphocytic infiltration of the skin by CD4+ lymphocytes in a dose-dependent manner with a maximum response at 1 microg/ml. Additionally, TARC/CCL17 induced interleukin-4 mRNA but not interferon-gamma mRNA expression in the skin, suggesting that the lymphocytes invading the skin are Th2 cells. Additionally, TARC/CCL17 induced its own production in the keratinocytes along with cutaneous T-cell-attracting chemokine (CTACK/CCL27) mRNA. We, therefore, conclude that TARC/CCL17 induces a Th2-dominated inflammatory reaction when injected into the skin.
Vestergaard
Christian
C
Department of Dermatology, Marselisborg Research Center, Research Laboratory D, Aarhus, Denmark. chr-vest@post9.tele.dk
Deleuran
Mette
M
Gesser
Borbala
B
Larsen
Christian Grønhøj
CG
D000818:Animals; D001483:Base Sequence; D054414:Chemokine CCL17; D018925:Chemokines / Q000235:genetics; D019742:Chemokines, CC / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics; D004247:DNA / Q000235:genetics; D003876:Dermatitis, Atopic / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology
C106230:CCL17 protein, human; C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D004247:DNA