serval:BIB_222C8B8C2A22
Manifold Roles of CCR7 and Its Ligands in the Induction and Maintenance of Bronchus-Associated Lymphoid Tissue.
10.1016/j.celrep.2018.03.072
000430384900013
29669284
Fleige
H.
author
Bosnjak
B.
author
Permanyer
M.
author
Ristenpart
J.
author
Bubke
A.
author
Willenzon
S.
author
Sutter
G.
author
Luther
S.A.
author
Förster
R.
author
article
2018-04-17
Cell reports
2211-1247
journal
23
3
783-795
The processes underlying the development and maintenance of tertiary lymphoid organs are incompletely understood. Using a Ccr7 knockout/knockin approach, we show that spontaneous bronchus-associated lymphoid tissue (BALT) formation can be caused by CCR7-mediated migration defects of dendritic cells (DCs) in the lung. Plt/plt mice that lack the CCR7 ligands CCL19 and CCL21-serine do not form BALT spontaneously because lung-expressed CCL21-leucine presumably suffices to maintain steady-state DC egress. However, plt/plt mice are highly susceptible to modified vaccinia virus infection, showing enhanced recruitment of immune cells as well as alterations in CCR7-ligand-mediated lymphocyte egress from the lungs, leading to dramatically enhanced BALT. Furthermore, we identify two independent BALT homing routes for blood-derived lymphocytes. One is HEV mediated and depends on CCR7 and L-selectin, while the second route is via the lung parenchyma and is independent of these molecules. Together, these data provide insights into CCR7/CCR7-ligand-orchestrated aspects in BALT formation.
Animals
Antibodies, Monoclonal/immunology
Bone Marrow Cells/cytology
Bronchi/cytology
Chemokine CCL19/deficiency
Chemokine CCL19/genetics
Chemokine CCL19/metabolism
Chemokine CCL21/metabolism
Dendritic Cells/cytology
Dendritic Cells/metabolism
L-Selectin/immunology
L-Selectin/metabolism
Ligands
Lung/cytology
Lung/immunology
Lung/metabolism
Lymphocytes/cytology
Lymphocytes/immunology
Lymphocytes/virology
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Fluorescence
Receptors, CCR7/deficiency
Receptors, CCR7/genetics
Receptors, CCR7/metabolism
Vaccinia virus/physiology
BALT
CCL21
CCR7
DCs
HEVs
MVA
plt/plt
eng
60_published
true
peer-reviewed
Publication types: Journal Article
Publication Status: ppublish
University of Lausanne
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