Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice.
Thymus- and activation-regulated chemokine (TARC; CCL17) is a lymphocyte-directed CC chemokine that specifically chemoattracts CC chemokine receptor 4-positive (CCR4(+)) Th2 cells. To establish the pathophysiological roles of TARC in vivo, we investigated here whether an mAb against TARC could inhibit the induction of asthmatic reaction in mice elicited by OVA. TARC was constitutively expressed in the lung and was up-regulated in allergic inflammation. The specific Ab against TARC attenuated OVA-induced airway eosinophilia and diminished the degree of airway hyperresponsiveness with a concomitant decrease in Th2 cytokine levels. Our results for the first time indicate that TARC is a pivotal chemokine for the development of Th2-dominated experimental allergen-induced asthma with eosinophilia and AHR. This study also represents the first success in controlling Th2 cytokine production in vivo by targeting a chemokine.
Kawasaki
S
S
Department of Respiratory Medicine, School of Medicine, University of Tokyo, Tokyo, Japan.
Takizawa
H
H
Yoneyama
H
H
Nakayama
T
T
Fujisawa
R
R
Izumizaki
M
M
Imai
T
T
Yoshie
O
O
Homma
I
I
Yamamoto
K
K
Matsushima
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000918:Antibody Specificity; D001249:Asthma / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004195:Disease Models, Animal; D007106:Immune Sera / Q000008:administration & dosage / Q000494:pharmacology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000517:prevention & control; D012333:RNA, Messenger / Q000096:biosynthesis; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; D019742:Chemokines, CC; D016207:Cytokines; D007106:Immune Sera; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D010047:Ovalbumin