Altered phenotype and functionality of circulating immune cells characterize adult patients with nonalcoholic steatohepatitis |
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Authors: | Inzaugarat María Eugenia Ferreyra Solari Nazarena Eugenia Billordo Luis Ariel Abecasis Raquel Gadano Adrian C Cherñavsky Alejandra Claudia |
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Institution: | (1) Laboratorio de Inmunogen?tica, Hospital de Cl?nicas “Jos? de San Mart?n”, Universidad de Buenos Aires, Av. C?rdoba 2351. 3er piso, 1120 Buenos Aires, Argentina;(2) Unidad de Hepatolog?a, Hospital Municipal de Gastroenterolog?a “Dr. C.B. Udaondo”, Buenos Aires, Argentina;(3) Secci?n de Hepatolog?a y Transplante Hep?tico, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; |
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Abstract: | Nonalcoholic steatohepatitis (NASH) is a chronic inflammatory liver disease associated with insulin resistance and its metabolic
consequences. Leukocyte mobilization, intrahepatic activation, and an exacerbated production of reactive oxygen species (ROS)
and cytokines contribute to the development of NASH. Though alterations in peripheral blood (PB) T cell proportions and functionality
remain unidentified, they might play a main role in NASH progression. We have compared the phenotype and Th1/Th2 commitment
of peripheral immune cell reservoirs in adult patients and controls as well as the ability of neutrophils and monocytes to
handle an ex vivo challenge. Also, we correlated those parameters with the main histological characteristics in NASH. Compared
with controls, patients showed increased numbers of CD4+ cells and both CD4+ and CD8+ CD45RO subsets together with a higher frequency of IFN-γ-producing CD4+ and CD8+ T cells. We also found a decreased number of CD4+ and CD8+ CD45RA subsets. The distinctive production of IFN-γ highlights the significance of the observed skewed frequencies of PB
T cells. Whereas ROS production by monocytes from NASH patients did not differ from controls, circulating neutrophils displayed
a particularly higher phorbol myristate acetate-induced production of ROS. A negative correlation between oxidative burst
and fibrosis grade was observed. This study reveals the presence of a characteristic profile of peripheral immune cells in
NASH. We also discuss the probable influence of obesity on some of our present findings. |
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