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; BENAVIDEZ JAVIER; ALEGRE NADIA S.; A. C. CHERÑAVSKY; COLOMBATO LUIS; CECILIA GARCIA; PONCINO DANIEL; BILLORDO LA
Lugar:
Roma
Reunión:
Workshop; Target-oriented apprioach to diagnosis and pharmacotherapy of NASH: a dialoque beween academia and industria; 2017
Institución organizadora:
Eur. Assoc for the study of Liver Diseases
Resumen:
T cells play a key role for the progress of nonalcoholic fatty liver diseases (NAFLD). Signaling through toll-like receptors (TLR) co-stimulates the activation, differentiation and generation of memory T cells. No study correlates clinical facts in NAFLD with TLR9 expression and function of adaptive cells. To study the potential link between metabolic changes and TLR9 expression in adaptive T cells from the periphery and the liver and, at the functional level, the consequences of TLR9 expression on the costimulatory activity and the generation of memory T cells in the periphery.Blood and liver samples came from 13 patients with simple steatosis (SS), 15 steatohepatitis (SH) and 21 controls (CO). Body mass index, waist circumference, total serum triglyceride and cholesterol (mg/dl), fasting blood glucose (mg/dL) serum alanine and aspartic aminotransferase activities (ALT/AST) (IU/l) were measured. From peripheral blood mononuclear cells (PBMC), CD3+ cells were negatively selected using immunobeads and stimulated with anti-CD3 (250 ng/ml) +/- CpG-OdN (2 uM). Cell suspensions were obtained by mechanical treatment of liver biopsies. Cells were stained with anti-CD4, -CD8, -TLR9, -CD69 or -IFN mAbs and studied by flow cytometry. The frequency of CCR7- cells was calculated as a ratio within CD4+ or CD8+ CD45RO cells. TLR9 expression was calculated with the index: [TLR9 expression CCR7- / TLR9 expression CCR7+ + CCR7-]. Mann-Whitney, Kruskal-Wallis and Spearman´s correlation tests were used. Within patients with NAFLD, we found a correlation between plasma levels of AST and ALT with TLR9 expression in peripheral CD8+ cells (r=0.645, p=0.037; r=0.645, p=0.034) and between plasma triglyceride levels with TLR9 expression in hepatic CD4+ cells (p=0.034, r=0.821). Patients with SS showed a decreased expression of TLR9 (CD4+: p=0.022, CD8+: p=0.002; vs. CO) and a lower frequency of differentiated CD8+ IFN+-producing cells (p=0.002, vs. SH) in periphery, together with a decreased expression of TLR9 (CD4: p=0.020; vs. CO) in liver. A higher frequency of CD4+CCR7- cells (p=0.013, vs. CO) was found but unrelated to a higher expression of TLR9 in CCR7- cells. A global decrease of TLR9 expression in adaptive cells is linked to characteristic metabolic changes associated with NAFLD. The relation between T cell activation and TLR9 expression evidences its protective role against an increased differentiation of CD8+ cells at early stages of NAFLD progression.