Author:
Riffard Clémence,Letaïef Laïla,Azar Safa,Casrouge Armanda,Brunet Isabelle,Teillaud Jean-Luc,Dieu-Nosjean Marie-Caroline
Abstract
AbstractTertiary lymphoid structures (TLS) are lymphoid organs present in inflammatory non-lymphoid tissues. Studies have linked TLS to favorable outcomes for patients with cancers or infectious diseases, but the mechanisms underlying their formation are not fully understood. In particular, secondary lymphoid organs innervation raises the question of sympathetic nerve fibers involvement in TLS organogenesis. We established a model of pulmonary inflammation based on 5 daily intranasal instillations of lipopolysaccharide (LPS) in immunocompetent mice. In this setting, lung lymphoid aggregates formed transiently, evolving toward mature TLS and disappearing when inflammation resolved. Sympathetic nerve fibers were then depleted using 6-hydroxydopamine. TLS quantification by immunohistochemistry showed a decrease in LPS-induced TLS number and surface in denervated mouse lungs. Although a reduction in alveolar space was observed, it did not impair overall pulmonary content of transcripts encoding TNF-α, IL-1β and IFN-γ inflammation molecules whose expression was induced by LPS instillations. Immunofluorescence analysis of immune infiltrates in lungs of LPS-treated mice showed a drop in the proportion of CD23+ naive cells among CD19+ B220+ B cells in denervated mice whereas the proportion of other cell subsets remained unchanged. These data support the existence of neuroimmune crosstalk impacting lung TLS neogenesis and local naive B cell pool.
Funder
Institut National de la Santé et de la Recherche Médicale
Association pour la Recherche sur le Cancer
Ligue Contre le Cancer
Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation
Agence Nationale de la Recherche
Collège de France
Fondation Leducq
Université de Recherche Paris Sciences et Lettres
Centre National de la Recherche Scientifique
Sorbonne Université
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
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