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dc.contributor.authorGrabarz, Felipe
dc.contributor.authorAguiar, Cristhiane Favero
dc.contributor.authorCorrea-Costa, Matheus
dc.contributor.authorBraga, Tarcio Teodoro
dc.contributor.authorHyane, Meire Ioshie [UNIFESP]
dc.contributor.authorAndrade-Oliveira, Vinicius
dc.contributor.authorLandgraf, Maristella de Almeida [UNIFESP]
dc.contributor.authorCâmara, Niels Olsen Saraiva [UNIFESP]
dc.identifier.citationInflammopharmacology. Basel, v. 26, n. 2, p. 491-504, 2018.
dc.description.abstractPulmonary fibrosis is a result of an abnormal wound healing in lung tissue triggered by an excessive accumulation of extracellular matrix proteins, loss of tissue elasticity, and debit of ventilatory function. NKT cells are a major source of Th1 and Th2 cytokines and may be crucial in the polarization of M1/M2 macrophages in pulmonary fibrogenesis. Although there appears to be constant scientific progress in that field, pulmonary fibrosis still exhibits no current cure. From these facts, we hypothesized that NKT cells could influence the development of pulmonary fibrosis via modulation of macrophage activation. Wild type (WT) and NKT type I cell-deficient mice (J alpha 18(-/-)) were subjected to the protocol of bleomycin-induced pulmonary fibrosis with or without treatment with NKT cell agonists alpha-galactosylceramide and sulfatide. The participation of different cell populations, collagen deposition, and protein levels of different cytokines involved in inflammation and fibrosis was evaluated. The results indicate a benign role of NKT cells in J alpha 18(-/-) mice and in wild-type alpha-galactosylceramide-sulfatide-treated groups. These animals presented lower levels of collagen deposition, fibrogenic molecules such as TGF-beta and vimentin and improved survival rates. In contrast, WT mice developed a Th2-driven response augmenting IL-4, 5, and 13 protein synthesis and increased collagen deposition. Furthermore, the arginase-1 metabolic pathway was downregulated in wild-type NKT-activated and knockout mice indicating lower activity of M2 macrophages in lung tissue. Hence, our data suggest that NKT cells play a protective role in this experimental model by down modulating the Th2 milieu, inhibiting M2 polarization and finally preventing fibrosis.en
dc.publisherSpringer Basel Ag
dc.rightsAcesso restrito
dc.subjectNatural killer T cellsen
dc.subjectAlveolar macrophagesen
dc.titleProtective role of NKT cells and macrophage M2-driven phenotype in bleomycin-induced pulmonary fibrosisen
dc.description.affiliationUniv Sao Paulo, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Lab Hypertens, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Div Nephrol, Lab Clin & Expt Immunol, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Biomed Sci 4, Ave Prof Lineu Prestes 1730, BR-05508000 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Div Nephrol, Lab Clin & Expt Immunol, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.citation.volumev. 26

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