INIGEM   23989
INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
LOW TLR9 EXPRESSION IN ADAPTIVE CELLS PROTECTS AGAINST PROGRESSION OF NONALCOHOLIC FATTY LIVER DISEASES
Autor/es:
GARCIA DANIEL; BAZ PLACIDA; A CHERÑAVSKY; COLOMBATO LUIS; CECILIA GARCIA; PONCINO DANIEL; ALEGRE NADIA S.
Reunión:
Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017
Institución organizadora:
Sociedades de Biociencias
Resumen:
T cells play a key role for the progression of Nonalcoholic Fatty Liver Diseases (NAFLD). Signaling through toll-like receptors (TLR) co-stimulates activation/ differentiation and generation of memory T cells. No study correlates clinical facts of NAFLD patients with TLR9 expression and functionality of adaptive cells. We aimed to study TLR9 expression in peripheral and liver adaptive cells during NAFLD progression, its link with metabolic changes and the differentiation of effector and memory cells. Biochemical/anthropometric parameters were measured. PBMC were obtained by Ficoll-hypaque gradient and liver cell suspensions by mechanical disruption. Cells were stained with anti-CD4, -CD8, -TLR9 or -IFNmAbs and studied by flow cytometry (FC). Analysis of CCR7+/- subpopulations of CD4+ and CD8+ memory cells was performed after negative selection of CD45RO cells. Mann-Whitney, Kruskal-Wallis and Spearman´s correlation tests were used. Blood and liver samples came from 13 patients with simple steatosis (SS), 15 steatohepatitis (SH) and 21 healthy controls (CO). We found a correlation between plasmatic AST and ALT levels with TLR9 expression in peripheral CD8+ cells (r=0.645, p=0.037; r=0.645, p=0.034), and between plasma triglycerides levels with TLR9 expression in hepatic CD4+ cells (p=0.034, r=0.821) from NAFLD patients. Liver CD4+ cells (p=0,020) and peripheral CD4+ and CD8+ cells from SS patients showed a low TLR9 expression vs. CO (p=0.022; p=0.002). CD8+ cells from SS patients exhibited a low frequency of CD8+IFN+ cells (p=0.002, vs. SH). A higher frequency of CD4+CCR7- cells (p=0.013, vs. CO) was found but unrelated to a higher expression of TLR9 in the CCR7+ and CCR7- cells. The overall lesser expression of TLR9 and particularly its association with cytotoxic cells differentiation in SS, but not with memory cell generation, might confer protection against NAFLD progression.