Up-regulation of CCL17, CCL22 and CCR4 in drug-induced maculopapular exanthema

• Published in: Clinical and experimental allergy Vol. 37; no. 5; pp. 704 - 713
• Main Authors: Tapia, B., Morel, E., Martín-Díaz, M.-Á., Díaz, R., Alves-Ferreira, J., Rubio, P., Padial, A., Bellón, T.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-05-2007; Blackwell
• Subjects: Allergic diseases; Biological and medical sciences; CCL17; CCL22; Chemokine CCL17; Chemokine CCL22; chemokines; Chemokines, CC - metabolism; drug allergy; Drug Eruptions - immunology; Exanthema - chemically induced; Exanthema - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunopathology; lymphocyte migration; Lymphocytes - immunology; Medical sciences; Receptors, CCR4; Receptors, Chemokine - genetics; Receptors, Chemokine - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - genetics; skin; Skin - immunology; Up-Regulation - immunology; Drug; Immunopathology; Allergy; Skin disease; CCL22; drug allergy; Exanthema; Migration; skin; Chemokine receptor; CC chemokine; chemokines; CCR4 chemokine receptor; Immunology; Lymphocyte; CCL17; lymphocyte migration
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2007.02699.x

Summary
Background
Maculopapular exanthema has been reported to be the most frequently drug‐induced cutaneous reaction. Although T lymphocytes are involved in the pathomechanism of this disease, little is know about the recruitment of these cells to the skin.
Objective
The aim of this work is to study the role of the chemokines TARC/CCL17 and MDC/CCL22 in the lymphocyte trafficking to affected skin in drug‐induced exanthemas.
Methods
Real‐time PCR was performed to quantify gene expression levels of CCL17, CCL22 and their receptor CCR4 in lesional skin biopsies and in peripheral blood mononuclear cells from patients. CCL27 and CCL22 proteins were detected in the skin by immunochemistry. Protein expression of CCR4 was determined by flow cytometry in peripheral blood lymphocytes. Functional migration assays to CCL17 and CCL22 were assessed to compare the migratory responses of peripheral blood lymphocytes from patients and healthy subjects.
Results
CCL17 and CCL22 were up‐regulated in maculopapular exanthema‐affected skin. CCR4 mRNA levels and protein expression were increased in peripheral blood mononuclear cells during the acute phase of the disease. The increased expression of the receptor was consistent with a higher response of peripheral blood lymphocytes to CCL17 and CCL22 compared with the migratory response in healthy donors.
Conclusion
TARC/CCL17 and MDC/CCL22 might cooperate in attracting T lymphocytes to skin in drug‐induced maculopapular exanthemas.