Elevated CCR6+ CD4+ T lymphocytes in tissue compared with blood and induction of CCL20 during the asthmatic late response.
CCR6 is expressed by multiple leucocyte subsets, including peripheral blood memory T cells, and mouse models implicate a role for this receptor in diverse inflammatory responses that include allergic airway disorders, inflammatory bowel disease and autoimmune encephalitis. In order to study the role of CCR6 in humans, we have investigated the patterns of CCR6 expression and function on T cells from the peripheral blood, skin, nose and lung, in health and in allergic disease. Results show that CCR6 was expressed consistently on a higher proportion of tissue versus peripheral blood-derived CD4+ T cells (P < 0.01). CCR6 was expressed predominantly on CD4+ compared with CD8+ cells in both blood- and tissue-derived T cells (P < 0.001). The number of cells showing CCR6 expression was not proportionally greater in peripheral blood or nasal mucosal T cells of subjects with symptomatic allergic rhinitis. CCR6+ cells demonstrated enhanced functional responses to CCL20 and CCL20 was increased in bronchoalveolar lavage fluid of asthmatics following endobronchial allergen provocation (P < 0.05). Thus, CCR6 may be important in the regulation of T cell recruitment to tissue and up-regulation of CCL20 expression may contribute to the recruitment and/or retention of effector T cells in allergic asthma.
Francis
J N
JN
Section of Allergy and Clinical Immunology, Imperial College London, London, UK.
Sabroe
I
I
Lloyd
C M
CM
Durham
S R
SR
Till
S J
SJ
D000328:Adult; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D001980:Bronchi / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000276:immunology / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D005260:Female; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000276:immunology; D054399:Receptors, CCR6 / Q000378:metabolism*; D012867:Skin / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000485:Allergens; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D054399:Receptors, CCR6