Manifold Roles of CCR7 and Its Ligands in the Induction and Maintenance of Bronchus-Associated Lymphoid Tissue

Cell Rep. 2018 Apr 17;23(3):783-795. doi: 10.1016/j.celrep.2018.03.072.


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.

Keywords: BALT; CCL21; CCR7; DCs; HEVs; MVA; plt/plt.

MeSH terms

  • 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


  • Antibodies, Monoclonal
  • Ccl19 protein, mouse
  • Ccr7 protein, mouse
  • Chemokine CCL19
  • Chemokine CCL21
  • Ligands
  • Receptors, CCR7
  • L-Selectin