Regulatory Role of Lymphoid Chemokine CCL19 and CCL21 in the Control of Allergic Rhinitis

• Published in: The Journal of immunology (1950) Vol. 179; no. 9; pp. 5897 - 5906
• Main Authors: Takamura, Kaoru, Fukuyama, Satoshi, Nagatake, Takahiro, Kim, Dong-Young, Kawamura, Aya, Kawauchi, Hideyuki, Kiyono, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.11.2007
• Subjects: Animals; Cell Differentiation; Chemokine CCL19 - genetics; Chemokine CCL19 - metabolism; Chemokine CCL21 - genetics; Chemokine CCL21 - metabolism; Dendritic Cells - cytology; DNA - genetics; Hypersensitivity - metabolism; Hypersensitivity - pathology; Immunoglobulin E - biosynthesis; Immunoglobulin E - immunology; Lymphocyte Count; Lymphoid Tissue - metabolism; Mice; Mice, Inbred BALB C; Rhinitis - metabolism; Rhinitis - pathology; T-Lymphocytes, Regulatory - cytology; Th1 Cells - metabolism; Th2 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.179.9.5897

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.