TY - JOUR T1 - Short-range interactions between fibrocytes and CD8<sup>+</sup> T cells in COPD bronchial inflammatory response JF - bioRxiv DO - 10.1101/2022.10.21.513138 SP - 2022.10.21.513138 AU - Edmée Eyraud AU - Elise Maurat AU - Jean-Marc Sac-Epée AU - Pauline Henrot AU - Maeva Zysman AU - Pauline Esteves AU - Thomas Trian AU - Hugues Bégueret AU - Pierre-Oliver Girodet AU - Matthieu Thumerel AU - Romain Hustache-Castaing AU - Roger Marthan AU - Florian Levet AU - Pierre Vallois AU - Cécile Contin-Bordes AU - Patrick Berger AU - Isabelle Dupin Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/10/21/2022.10.21.513138.abstract N2 - The peri-bronchial zone of chronic obstructive pulmonary disease (COPD) is the site of extensive infiltration of immune cell, allowing persistent contacts between resident cells and immune cells. Tissue fibrocytes interaction with CD8+ T cells and its consequences were investigated. We show that interactions beween both cell types are more frequent in distal airways from COPD patients compared to those of control subjects. Tissular CD8+ T cells from COPD patients promote fibrocyte chemotaxis via the CXCL8-CXCR1/2 axis. CD8+ T cells establish short-term interactions with fibrocytes, that trigger CD8+ T cell proliferation in a CD54- and CD86-dependent manner, as well as pro-inflammatory cytokines production. A computational model accurately predicts histological ex vivo characteristics and allows to monitors disease evolution. Overall, our study reveals that local interactions between fibrocytes and CD8+ T cells may comromise the balance between protective immunity and chronic inflammation in bronchi of COPD patients.Teaser Fibrocytes/CD8+ T cells interactions cause inflammation through a maintained pathophysiological loop in bronchi of COPD patients.Competing Interest StatementPB, POG, ID have a patent (EP 3050574: Use of plerixafor for treating and/or preventing acute exacerbations of chronic obstructive pulmonary disease) granted. MZ reports grants from AstraZeneca ; grants Fondation Bordeaux Universite, with funding from Assistance Ventilatoire a Domicile (AVAD) and Federation Girondine de Lutte contre les Maladies Respiratoires (FGLMR) and personal fees from AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, GlaxoSmithKline and non-financial support Lilly outside the submitted work; POG reports grants, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Chiesi, personal fees and non-financial support from GlaxoSmithKline, personal fees and non-financial support from Novartis, personal fees and non-financial support from Sanofi, outside the submitted work; PB reports grants from AstraZeneca, Glaxo-Smith-Kline, Novartis, Chiesi, which support COBRA during the conduct of the study; grants and personal fees from AstraZeneca, BoehringerIngelheim, Novartis, personal fees and non-financial support from Chiesi, Sanofi, Menarini, outside the submitted work; ID and PH report grants from the Fondation Bordeaux Universite, with funding from Assistance Ventilatoire a Domicile (AVAD) and Federation Girondine de Lutte contre les Maladies Respiratoires" (FGLMR) during the conduct of the study. ER -