Role of CXC chemokine ligand 13, CC chemokine ligand (CCL) 19, and CCL21 in the organization and function of nasal-associated lymphoid tissue.
Nasal-associated lymphoid tissue (NALT) orchestrates immune responses to Ags in the upper respiratory tract. Unlike other lymphoid organs, NALT develops independently of lymphotoxin-alpha (LTalpha). However, the structure and function of NALT are impaired in Ltalpha(-/-) mice, suggesting a link between LTalpha and chemokine expression. In this study we show that the expression of CXCL13, CCL19, CCL21, and CCL20 is impaired in the NALT of Ltalpha(-/-) mice. We also show that the NALT of Cxcl13(-/-) and plt/plt mice exhibits some, but not all, of the structural and functional defects observed in the NALT of Ltalpha(-/-) mice. Like the NALT of Ltalpha(-/-) mice, the NALT in Cxcl13(-/-) mice lacks follicular dendritic cells, BP3(+) stromal cells, and ERTR7(+) lymphoreticular cells. However, unlike the NALT of Ltalpha(-/-) mice, the NALT of Cxcl13(-/-) mice has peripheral node addressin(+) high endothelial venules (HEVs). In contrast, the NALT of plt/plt mice is nearly normal, with follicular dendritic cells, BP3(+) stromal cells, ERTR7(+) lymphoreticular cells, and peripheral node addressin(+) HEVs. Functionally, germinal center formation and switching to IgA are defective in the NALT of Ltalpha(-/-) and Cxcl13(-/-) mice. In contrast, CD8 T cell responses to influenza are impaired in Ltalpha(-/-) mice and plt/plt mice. Finally, the B and T cell defects in the NALT of Ltalpha(-/-) mice lead to delayed clearance of influenza from the nasal mucosa. Thus, the B and T cell defects in the NALT of Ltalpha(-/-) mice can be attributed to the impaired expression of CXCL13 and CCL19/CCL21, respectively, whereas impaired HEV development is directly due to the loss of LTalpha.
Rangel-Moreno
Javier
J
Trudeau Institute, Saranac Lake, NY 12983, USA.
Moyron-Quiroz
Juan
J
Kusser
Kim
K
Hartson
Louise
L
Nakano
Hideki
H
Randall
Troy D
TD
D000818:Animals; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000502:physiology*; D019743:Chemokines, CXC / Q000235:genetics / Q000502:physiology*; D004729:Endothelium, Lymphatic / Q000033:anatomy & histology / Q000276:immunology / Q000378:metabolism; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D008233:Lymphotoxin-alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology
C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D008233:Lymphotoxin-alpha