title: Could T cells be involved in lung deterioration and hyperglycemia in cystic fibrosis?
abstract: Cystic fibrosis-related diabetes (CFRD) is the most frequent complication of cystic fibrosis (CF) and associated with increased mortality. Why patients have an accelerated loss of lung function before the diagnosis of CFRD remains poorly understood. We reported that patients with or without CFRD had increased glucose excursions when compared to healthy peers. Studies have demonstrated that patients with CF have increased glucose fluctuations and hyperglycemia and that this may affect the clinical course of CF and lead to lymphocyte dysfunction. T-helper 17 (Th17) lymphocytes produce and secrete the pro-inflammatory cytokine IL-17. The Th17 pathway is involved in CF lung inflammation, β-cell destruction in type 1 diabetes (T1D) and Th17 cells of patients with type 2 diabetes have increased production of IL-17 when compared to healthy peers. Also, regulatory T-cells (Tregs) have been shown to be dysfunctional and produce IL-17 in T1D. Furthermore, vitamin D can affect inflammation in CF, diabetes and the differentiation of lymphocytes. In this review, we discuss the potential roles of hyperglycemia on Th17 cells, Tregs and IL-17 as a potential cause for accelerated lung function decline before CFRD and how this could be modulated by vitamin D or by directly intervening in the IL-17A pathway.
authors.affiliation: Nutrition Department, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Québec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Ziai
authors.affiliation: Nutrition Department, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Québec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Coriati
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Québec, Canada.
authors.forename: M-S
authors.initials: MS
authors.lastname: Gauthier
authors.affiliation: Nutrition Department, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Québec, Canada; Montreal Diabetes Research Centre (MDRC), Montréal, Québec, Canada; Cystic Fibrosis Clinic, Centre Hospitalier de l'Université de Montréal (CHUM) & CHUM Research Center (CR-CHUM), Montréal, Québec, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Rabasa-Lhoret
authors.affiliation: Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada. Electronic address: Martin.Richter@USherbrooke.ca.
authors.forename: M V
authors.initials: MV
authors.lastname: Richter
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000150:complications*; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology*; D020381:Interleukin-17 / Q000502:physiology; D008171:Lung Diseases / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D058504:Th17 Cells / Q000502:physiology*
chemical_list: D020381:Interleukin-17
keywords: Cystic fibrosis-related diabetes; Hyperglycemia; IL-17 therapy; Lung function; Regulatory T-cells; Th17 cells