A critical role for dendritic cells in the evolution of IL-1β-mediated murine airway disease

The Journal of Immunology : Official Journal of the American Association of Immunologists
Mitsuo HashimotoStephen L Nishimura

Abstract

Chronic airway inflammation and fibrosis, known as airway remodeling, are defining features of chronic obstructive pulmonary disease and are refractory to current treatments. How and whether chronic inflammation contributes to airway fibrosis remain controversial. In this study, we use a model of chronic obstructive pulmonary disease airway disease utilizing adenoviral delivery of IL-1β to determine that adaptive T cell immunity is required for airway remodeling because mice deficient in α/β T cells (tcra(-/-)) are protected. Dendritic cells (DCs) accumulate around chronic obstructive pulmonary disease airways and are critical to prime adaptive immunity, but they have not been shown to directly influence airway remodeling. We show that DC depletion or deficiency in the crucial DC chemokine receptor ccr6 both protect from adenoviral IL-1β-induced airway adaptive T cell immune responses and fibrosis in mice. These results provide evidence that chronic airway inflammation, mediated by accumulation of α/β T cells and driven by DCs, is critical to airway fibrosis.

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Citations

Dec 4, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Haruhiko YanagisawaStephen L Nishimura
Jul 27, 2017·Expert Review of Respiratory Medicine·Mathew Suji EapenSukhwinder Singh Sohal
Jun 26, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mitsuo HashimotoStephen L Nishimura
Apr 29, 2015·The Journal of Biological Chemistry·Oliver J BrandStephen L Nishimura
Apr 5, 2021·Paediatric Respiratory Reviews·Jered WeinstockDeepa Rastogi

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