title: Size and dynamics of mucosal and peripheral IL-17A+ T-cell pools in pediatric age, and their disturbance in celiac disease.
abstract: Mucosal interleukin (IL)-17A-producing T cells contribute to protective antimicrobial responses and to epithelial barrier integrity; their role in celiac disease (CD) is debated. We analyzed the frequency and developmental dynamics of mucosal (intraepithelial lymphocytes (IEL)) and circulating (peripheral blood (PB)) IL-17A (T17) and/or interferon (IFN)-γ-producing (T1, T1/T17) T-cell populations in 86 pediatric controls and 116 age-matched CD patients upon phorbol myristate acetate/ionomycin or CD3/CD28 stimulation. T17 and T1/17 are physiologically present among IEL and PB populations, and their frequency is selectively and significantly reduced in CD IEL. The physiological age-dependent increase of Th17 IEL is also absent in CD, while IFN-γ-producing PB-T cells significantly accumulate with patient's age. Finally, the amplitude of IL-17A+ and IFN-γ+ T-cell pools are significantly correlated in different individuals; this relationship only applies to CD4+ T cells in controls, while it involves also the CD4- counterpart in CD patients. In conclusion, both size and dynamics of mucosa-associated and circulating IL-17A+ T-cell pools are finely regulated in human pediatric subjects, and severely disturbed in CD. The impaired IL-17A+ IEL-T pool may negatively impact on epithelial barrier efficiency, and contribute to CD mucosa damage; the disturbed dynamics of circulating IL-17A+ and IFN-γ+ T-cell pools may be involved in the extraintestinal autoimmune manifestations associated with CD.
authors.affiliation: Department of Experimental Medicine, Sapienza University, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: La Scaleia
authors.forename: M
authors.initials: M
authors.lastname: Barba
authors.forename: G
authors.initials: G
authors.lastname: Di Nardo
authors.forename: M
authors.initials: M
authors.lastname: Bonamico
authors.forename: S
authors.initials: S
authors.lastname: Oliva
authors.forename: R
authors.initials: R
authors.lastname: Nenna
authors.forename: F
authors.initials: F
authors.lastname: Valitutti
authors.forename: M
authors.initials: M
authors.lastname: Mennini
authors.forename: M
authors.initials: M
authors.lastname: Barbato
authors.forename: M
authors.initials: M
authors.lastname: Montuori
authors.forename: A
authors.initials: A
authors.lastname: Porzia
authors.forename: L
authors.initials: L
authors.lastname: Petrarca
authors.forename: S
authors.initials: S
authors.lastname: Battella
authors.forename: S
authors.initials: S
authors.lastname: Cucchiara
authors.forename: M
authors.initials: M
authors.lastname: Piccoli
authors.forename: A
authors.initials: A
authors.lastname: Santoni
authors.forename: F
authors.initials: F
authors.lastname: Mainiero
authors.forename: G
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D001775:Blood Circulation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002446:Celiac Disease / Q000276:immunology*; D049109:Cell Proliferation; D002648:Child; D004386:Duodenum / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D007371:Interferon-gamma