title: Peripheral depletion of NK cells and imbalance of the Treg/Th17 axis in idiopathic pulmonary fibrosis patients.
abstract: The immune response plays an unsettled role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), the contribution of inflammation being controversial as well. Emerging novel T cell sub-populations including regulatory T lymphocytes (Treg) and interleukin (IL)-17 secreting T helper cells (Th17) may exert antithetical actions in this scenario. Phenotype and frequency of circulating immune cell subsets were assessed by multi-parametric flow cytometry in 29 clinically stable IPF patients and 17 healthy controls. The interplay between Treg lymphocytes expressing transforming growth factor (TGF)-β and Th17 cells was also investigated. Proportion and absolute number of natural killer (NK) cells were significantly reduced in IPF patients in comparison with controls (p<0.001). Conversely, the proportion and absolute number of CD3(+)CD4(+)CD25(high)Foxp-3(+) cells were significantly increased in IPF patients (p=0.000). As in controls, almost the totality of cells (>90%) expressed TGF-β upon stimulation. Interestingly, the frequency of Th17 cells was significantly compromised in IPF patients (p=0.000) leading to an increased TGF-β/IL-17 ratio (4.2±2.3 vs 0.5±0.3 in controls, p=0.000). Depletion of NK and Th17 cells along with a not compromised Treg compartment delineate the existence of an "immune profile" that argue against the recent hypothesis of IPF as an autoimmune disease. Our findings along with the imbalance of the Treg/Th17 axis more closely suggest these immune perturbations to be similar to those observed in cancer. Clinical relevance, limitations and perspectives for future research are discussed.
authors.affiliation: Dipartimento di Ematologia, IRCCS INT Fondazione Pascale, Napoli, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Galati
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Napoli, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: De Martino
authors.affiliation: UOSC Immunologia Oncologica, IRCCS INT Fondazione Pascale, Napoli, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Trotta
authors.affiliation: Dipartimento dei Servizi Diagnostici e Generali, Ospedali dei Colli, Monaldi-Cotugno-CTO, Napoli, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Rea
authors.affiliation: Dipartimento di Sanità Pubblica, Università Federico II, Napoli, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Bruzzese
authors.affiliation: Fisiopatologia Respiratoria, ASL, Salerno, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Cicchitto
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Napoli, Italy.
authors.forename: Anna Agnese
authors.initials: AA
authors.lastname: Stanziola
authors.affiliation: UOSC Immunologia Oncologica, IRCCS INT Fondazione Pascale, Napoli, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Napolitano
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Napoli, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sanduzzi
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Napoli, Italy. Electronic address: marialuisa.bocchino@unina.it.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Bocchino
mesh_terms: D000368:Aged; D017252:CD3 Complex / Q000096:biosynthesis; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000276:immunology* / Q000473:pathology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000097:blood / Q000276:immunology
chemical_list: D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta
keywords: Flow cytometry; IPF; NK cells; Regulatory T cells; Th17 cells