A sphingosine-1-phosphate receptor 1 agonist inhibits tertiary lymphoid tissue reactivation and hypersensitivity in the lung

Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell-rich tertiary lymphoid tissues (TLTs), which are alleged sites of amplification for antigen-specific responses. The sphingosine-1-phosphate receptor 1 (S1P ) regulates key mechanisms underlying lymphoid tissue biology...

Full description

Saved in:
Bibliographic Details
Published in:Mucosal immunology 2018-01, Vol.11 (1), p.112-119
Main Authors: Huppé, C A, Blais Lecours, P, Lechasseur, A, Gendron, D R, Lemay, A M, Bissonnette, E Y, Blanchet, M R, Duchaine, C, Morissette, M C, Rosen, H, Marsolais, D
Format: Article
Language:English
Subjects:
Agonists
Allergens - immunology
Alveolitis
Alveolitis, Extrinsic Allergic - drug therapy
Alveolitis, Extrinsic Allergic - immunology
Animals
Antibodies, Bacterial - blood
Antigens, Bacterial - immunology
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
Cell Movement
Chemokine CXCL13 - metabolism
CXCL13 protein
Disease Models, Animal
Enlargement
Female
Humans
Hypersensitivity
Lung - immunology
Lymph nodes
Lymphocyte Activation
Lymphocytes
Lymphocytes B
Lymphoid tissue
Lymphoid Tissue - drug effects
Lymphoid Tissue - immunology
Metal workers
Methanobacteriaceae - immunology
Mice
Mice, Inbred C57BL
Neutrophil Infiltration
Pneumonitis
Receptors, Lysosphingolipid - agonists
Receptors, Lysosphingolipid - metabolism
Sphingosine 1-phosphate
Sphingosine-1-Phosphate Receptors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell-rich tertiary lymphoid tissues (TLTs), which are alleged sites of amplification for antigen-specific responses. The sphingosine-1-phosphate receptor 1 (S1P ) regulates key mechanisms underlying lymphoid tissue biology and its chemical modulation causes lymphocyte retention in lymph nodes. Given the putative immunopathogenic impact of lymphocyte accumulation in TLTs, we investigated whether or not chemical modulation of S1P caused lymphocyte retention within TLTs in a model of hypersensitivity pneumonitis. Mice were exposed subchronically to Methanosphaera stadtmanae (MSS) in order to induce an hypersensitivity pneumonitis-like disease. MSS exposure induced B-cell-rich TLTs surrounded by S1P -positive microvessels. Upon MSS rechallenge, the S1P agonist RP001 prevented the pulmonary increase of CXCL13, a chief regulator of B-cell recruitment in lymphoid tissues. This was associated with a complete inhibition of MSS rechallenge-induced TLT enlargement and with a 2.3-fold reduction of MSS-specific antibody titers in the lung. Interference with TLT reactivation was associated with a 77% reduction of neutrophil accumulation and with full inhibition of protein-rich leakage in the airways. Thus, an S1P agonist hinders TLT enlargement upon antigenic rechallenge and inhibits key pathognomonic features of experimental hypersensitivity pneumonitis.
ISSN:1933-0219
1935-3456
DOI:10.1038/mi.2017.37