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Hepatic lymphocytes involved in the pathogenesis of pediatric and adult non-alcoholic fatty liver disease

2021; Nature Portfolio; Volume: 11; Issue: 1 Linguagem: Inglês

10.1038/s41598-021-84674-z

2045-2322

Victoria Cairoli, Elena De Matteo, D Rios, Carol Lezama, Marcela Galoppo, Paola Casciato, Eduardo Müllen, Cecilia Graciela Giadans, Gustavo M. Bertot, María Victoria Preciado, Pamela Valva,

Diabetes and associated disorders

Abstract The immune response is critical in NAFLD pathogenesis, but the liver infiltrate’s composition and the role of each T cell population is still up for debate. To characterize liver pathogenesis in pediatric and adult cases, frequency and localization of immune cell populations [Cytotoxic T Lymphocytes (CD8+), T helper Lymphocytes (CD4+), Regulatory T lymphocytes (Foxp3+) and Th17 (IL-17A+)] were evaluated. In portal/periportal (P/P) tracts, both age groups displayed a similar proportion of CD8+ and CD4+ lymphocytes. However, comparable Foxp3+ and IL-17A+ cell frequencies were observed in pediatric cases, meanwhile, in adults Foxp3+ was higher than IL-17A+ cells. Interestingly, IL-17A+ lymphocytes seemed to be nearly exclusive of P/P area in both age groups. In intralobular areas, both pediatric and adult cases showed CD8+ lymphocytes predominance with lower frequencies of CD4+ lymphocytes followed by Foxp3+ . Severe inflammation was associated with higher intralobular Foxp3+ lymphocytes ( p = 0.026) in children, and lower P/P Foxp3+ and higher IL-17A+ lymphocytes in adults. All cases with fibrosis ≥ 2 displayed P/P low Foxp3+ and high IL-17A+ lymphocyte counts. Pediatric cases with worse steatosis showed high P/P CD4+ ( p = 0.023) and intralobular CD8+ ( p = 0.027) and CD4+ cells ( p = 0.012). In NAFLD cases, the lymphocyte liver infiltrate composition differs between histological areas. Treg and Th17 balance seems to condition damage progression, denoting their important role in pathogenesis.