title: Expansion of cortical and medullary sinuses restrains lymph node hypertrophy during prolonged inflammation.
abstract: During inflammation, accumulation of immune cells in activated lymph nodes (LNs), coupled with a transient shutdown in lymphocyte exit, results in dramatic cellular expansion. Counter-regulatory measures to restrain LN expansion must exist and may include re-establishment of lymphocyte egress to steady-state levels. Indeed, we show in a murine model that egress of lymphocytes from LNs was returned to steady-state levels during prolonged inflammation following initial retention. This restoration in lymphocyte egress was supported by a preferential expansion of cortical and medullary sinuses during late inflammation. Cortical and medullary sinus remodeling during late inflammation was dependent on temporal and spatial changes in vascular endothelial growth factor-A distribution. Specifically, its expression was restricted to the subcapsular space of the LN during early inflammation, whereas its expression was concentrated in the paracortical and medullary regions of the LN at later stages. We next showed that this process was mostly driven by the synergistic cross-talk between fibroblastic reticular cells and interstitial flow. Our data shed new light on the biological significance of LN lymphangiogenesis during prolonged inflammation and further underscore the collaborative roles of stromal cells, immune cells, and interstitial flow in modulating LN plasticity and function.
authors.affiliation: Department of Microbiology, Immunology Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Kar Wai
authors.initials: KW
authors.lastname: Tan
authors.forename: Kim Pin
authors.initials: KP
authors.lastname: Yeo
authors.forename: Fiona H S
authors.initials: FH
authors.lastname: Wong
authors.forename: Hwee Ying
authors.initials: HY
authors.lastname: Lim
authors.forename: Kai Ling
authors.initials: KL
authors.lastname: Khoo
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Abastado
authors.forename: Véronique
authors.initials: V
authors.lastname: Angeli
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002450:Cell Communication; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006984:Hypertrophy; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007274:Injections, Intraperitoneal; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D042583:Lymphangiogenesis; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D042461:Vascular Endothelial Growth Factor A