Lymphotoxin-beta receptor signaling is required for the homeostatic control of HEV differentiation and function.
The lymphotoxin axis is important for the maintenance of several specialized lymphoid microenvironments in secondary lymphoid tissue. Lymphoid-tissue architecture is highly plastic and requires continual homeostatic signaling to maintain its basal functional state. The cellularity of lymph nodes in adult mice was reduced by systemic blockade of lymphotoxin-beta receptor (LTbeta R) signaling with a soluble decoy receptor both in resting and reactive settings. This reduction in cellularity resulted from greatly impaired lymphocyte entry into lymph nodes due to decreased levels of peripheral lymph node addressing (PNAd) and MAdCAM on high endothelial venules (HEV). LTbeta R signaling was required to maintain normal levels of RNA expression of MAdCAM, and also of PNAd by regulating the expression of key enzymes and scaffold proteins required for its assembly. Thus, the homeostatic maintenance of functional HEV status in adult mice relies largely on LTbeta R signaling.
Browning
Jeffrey L
JL
Department of Immunobiology, Biogen Idec, Cambridge, Massachusetts 02142, USA. jeff.browning@biogenidec.com
Allaire
Norm
N
Ngam-Ek
Apinya
A
Notidis
Evangelia
E
Hunt
Jane
J
Perrin
Steven
S
Fava
Roy A
RA
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D006706:Homeostasis; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D053259:Lymphotoxin beta Receptor; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D048069:Tumor Necrosis Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D000954:Antigens, Surface; C069886:L-selectin counter-receptors; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D048069:Tumor Necrosis Factors