Regulatory role of lymphoid chemokine CCL19 and CCL21 in the control of allergic rhinitis.
The lymphoid chemokines CCL19 and CCL21 are known to be crucial both for lymphoid cell trafficking and for the structural organization of lymphoid tissues such as nasopharynx-associated lymphoid tissue (NALT). However, their role in allergic responses remains unclear, and so our current study aims to shed light on the role of CCL19/CCL21 in the development of allergic rhinitis. After nasal challenge with OVA, OVA-sensitized plt (paucity of lymph node T cells) mice, which are deficient in CCL19/CCL21, showed more severe allergic symptoms than did identically treated wild-type mice. OVA-specific IgE production, eosinophil infiltration, and Th2 responses were enhanced in the upper airway of plt mice. Moreover, in plt mice, the number of CD4(+)CD25(+) regulatory T cells declined in the secondary lymphoid tissues, whereas the number of Th2-inducer-type CD8alpha(-)CD11b(+) myeloid dendritic cells (m-DCs) increased in cervical lymph nodes and NALT. Nasal administration of the plasmid-encoding DNA of CCL19 resulted in the reduction of m-DCs in the secondary lymphoid tissues and the suppression of allergic responses in plt mice. These results suggest that CCL19/CCL21 act as regulatory chemokines for the control of airway allergic disease and so may offer a new strategy for the control of allergic disease.
Takamura
Kaoru
K
Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Fukuyama
Satoshi
S
Nagatake
Takahiro
T
Kim
Dong-Young
DY
Kawamura
Aya
A
Kawauchi
Hideyuki
H
Kiyono
Hiroshi
H
D000818:Animals; D002454:Cell Differentiation; D054415:Chemokine CCL19 / Q000235:genetics / Q000378:metabolism*; D054421:Chemokine CCL21 / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology; D006967:Hypersensitivity / Q000378:metabolism / Q000473:pathology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D012220:Rhinitis / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D054415:Chemokine CCL19; D054421:Chemokine CCL21; D007073:Immunoglobulin E; D004247:DNA