CCR4 ligands are up-regulated in the airways of atopic asthmatics after segmental allergen challenge.
T-helper (Th) 2 cytokines are thought to mediate most features of allergic inflammation in atopic asthma. However, it remains unclear whether chemokine pathways direct selective recruitment of Th2 cells to the airways during human allergic responses. Bronchoalveolar lavage (BAL) was performed in 15 nonsmoking mild atopic asthmatics before and 24 h after a fibreoptic segmental allergen challenge, and chemokines related to T-cell recruitment were assayed by ELISA. The Th2-related C-C chemokine (CCR)4 ligands, macrophage-derived chemokine/C-C chemokine ligand (CCL)22 and thymus and activation-regulated chemokine/CCL17, were increased in BAL after challenge. These chemokines correlated significantly with lymphocyte numbers and with interleukin (IL)-5 and IL-13 in post-challenge BAL. In contrast, two out of three putative Th1-related chemokines did not change. There were no alterations in monokine induced by interferon (IFN)-gamma/CXC chemokine ligand (CXCL)9 or macrophage inflammatory protein-1alpha/CCL3; whereas a significant increase in IFN-induced protein-10kDa/CXCL10 was observed, which did not correlate with the T-cell influx. In peripheral mononuclear cells from atopic donors, CCL22 and CCL17 were induced by IL-4 and IL-13, further supporting the relationship between CCL22/CCL17 and Th2 cytokines. Finally, CCL22 was able to trigger actin polymerisation in peripheral CD4+ T-cells expressing CCR4. Thus, C-C chemokine receptor 4 ligands are up-regulated in the airways of atopic asthmatics following allergen exposure, contribute to the T-cell influx to the airways and are closely related to the Th2-cytokine response.
Pilette
C
C
Upper Respiratory Medicine, Imperial College London, National Heart & Lung Institute, London, UK.
Francis
J N
JN
Till
S J
SJ
Durham
S R
SR
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000276:immunology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008875:Middle Aged; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000378:metabolism*; D018709:Statistics, Nonparametric; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
C515354:CCR4 protein, human; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D007073:Immunoglobulin E