title: Nitric oxide and TNFα are critical regulators of reversible lymph node vascular remodeling and adaptive immune response.
abstract: Lymph node (LN) vascular growth, at the level of the main arteriole, was recently characterized for the first time during infection. Arteriole diameter was shown to increase for at least seven days and to occur via a CD4(+) T cell dependent mechanism, with vascular expansion playing a critical role in regulating induction of adaptive immune response. Here, using intravital microscopy of the inguinal LN during herpes simplex type II (HSV-2) infection, the data provides the first studies that demonstrate arteriole expansion during infection is a reversible vascular event that occurs via eutrophic outward remodeling. Furthermore, using genetic ablation models, and pharmacological blockade, we reveal arteriole remodeling and LN hypertrophy to be dependent upon both endothelial nitric oxide synthase (eNOS) and TNFα expression. Additionally, we reveal transient changes in nitric oxide (NO) levels to be a notable feature of response to viral infection and LN vascular remodeling and provide evidence that mast cells are the critical source of TNFα required to drive arteriole remodeling. Overall, this study is the first to fully characterize LN arteriole vascular changes throughout the course of infection. It effectively reveals a novel role for NO and TNFα in LN cellularity and changes in LN vascularity, which represent key advances in understanding LN vascular physiology and adaptive immune response.
authors.affiliation: Interdisciplinary Studies, University of Northern BC, Prince George, British Columbia, Canada.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Sellers
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Payne
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D015550:Cell Degranulation; D002522:Chlorocebus aethiops; D005260:Female; D006561:Herpes Simplex / Q000276:immunology / Q000503:physiopathology; D008198:Lymph Nodes / Q000098:blood supply* / Q000276:immunology / Q000503:physiopathology*; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014709:Vero Cells
chemical_list: D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D009543:Nifedipine; D019331:NG-Nitroarginine Methyl Ester