Chronic hepatitis C liver microenvironment: role of the Th17/Treg interplay related to fibrogenesis

• Published in: Scientific reports Vol. 7; no. 1; pp. 13283 - 9
• Main Authors: Rios, Daniela Alejandra, Valva, Pamela, Casciato, Paola Cecilia, Frias, Silvia, Soledad Caldirola, María, Gaillard, María Isabel, Bezrodnik, Liliana, Bandi, Juan, Galdame, Omar, Ameigeiras, Beatriz, Krasniansky, Diana, Brodersen, Carlos, Mullen, Eduardo, Matteo, Elena Noemí De, Preciado, María Victoria
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-10-2017; Nature Publishing Group
• Subjects: 13/1; 13/31; 13/51; 14/19; 14/63; 38; 38/77; 692/4020/4021/234/2513/1551; 692/420/2780; 692/699/255/234/2513/1551; Adult; Aged; Biomarkers; Biopsy; CD4 antigen; Cell Communication; Cellular Microenvironment - immunology; Female; Fibrosis; Fluorescent Antibody Technique; Foxp3 protein; Helper cells; Hepatitis; Hepatitis C; Hepatitis C, Chronic - immunology; Hepatitis C, Chronic - metabolism; Hepatitis C, Chronic - pathology; Hepatitis C, Chronic - virology; Humanities and Social Sciences; Humans; Immunohistochemistry; Immunophenotyping; Interferon; Interleukin 10; Interleukin 6; Liver; Liver Cirrhosis - etiology; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Liver Function Tests; Lymphocytes; Lymphocytes T; Male; Middle Aged; multidisciplinary; Pathogenesis; Peripheral blood; Science; Science (multidisciplinary); T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Th17 Cells - immunology; Th17 Cells - metabolism; Tumor necrosis factor-α; Viral Load
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-13777-3

The role of the different lymphocyte populations in liver microenvironment of chronic hepatitis C (CHC) patients is still matter of debate. Since Th17 and Treg have opposite functions, their balance could affect disease progression. The aim was to explore liver microenvironment and its peripheral blood counterpart in adult CHC patients. CD4
+
lymphocytes were predominant in the liver, with high Foxp3
+
but low IL-17A
+
frequency. IL-17A
+
lymphocytes and IL-17A
+
/Foxp3
+
ratio displayed association with advanced fibrosis (
p
 = 0.0130;
p
 = 0.0236, respectively), while Foxp3
+
lymphocytes and IL-10 expression level inversely correlated with fibrosis severity (
p
 = 0.0381,
p
 = 0.0398, respectively). TGF-β/IL-6 ratio correlated with IL-17A
+
/Foxp3
+
ratio (
p
 = 0.0036,
r
 = 0.5944) and with IL-17A
+
lymphocytes (
p
 = 0.0093;
r
 = 0.5203). TNF-α and TGF-β were associated with hepatitis severity (
p
 = 0.0409,
p
 = 0.0321). Peripheral blood lymphocyte frequency was not associated with liver damage. There are functionally different immune cell populations actively involved in liver damage, but the liver cytokine milieu actually drives the pathogenesis. The intrahepatic Foxp3
+
lymphocytes predominance beside the low IL-17A
+
lymphocytes frequency, delineate a skewed IL-17A
+
/Foxp3
+
balance towards Foxp3
+
lymphocytes. However, the IL-17A
+
lymphocytes association with advanced fibrosis denotes their role in the pathogenesis. Therefore, the interplay between Th17 and Treg conditions liver fibrogenesis.