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Progression from Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis Is Marked by a Higher Frequency of Th17 Cells in the Liver and an Increased Th17/Resting Regulatory T Cell Ratio in Peripheral Blood and in the Liver
- Source :
- The Journal of Immunology. 196:97-105
- Publication Year :
- 2016
- Publisher :
- The American Association of Immunologists, 2016.
-
Abstract
- Nonalcoholic fatty liver disease is increasing in prevalence. It can be subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Five to twenty percent of cases progress from NAFL to NASH. Increased hepatic Th17 cells and IL-17 expression were observed in NASH mice and patients, respectively. We analyzed CD4+ effector T cells and regulatory T cells (Tregs) from peripheral blood and livers of NAFL and NASH patients. A total of 51 NAFL patients, 30 NASH patients, 31 nonalcoholic fatty liver disease patients (without histology), and 43 healthy controls were included. FACS analysis was performed on PBMCs and intrahepatic lymphocytes. Compared with healthy controls, a lower frequency of resting Tregs (rTregs; CD4+CD45RA+CD25++) and higher frequencies of IFN-γ+ and/or IL-4+ cells were detected among CD4+ T cells of peripheral blood in NASH, and to a lesser degree in NAFL. In hepatic tissue, NAFL to NASH progression was marked by an increase in IL-17+ cells among intrahepatic CD4+ T cells. To define immunological parameters in peripheral blood to distinguish NAFL from NASH, we calculated different ratios. Th17/rTreg and Th2/rTreg ratios were significantly increased in NASH versus NAFL. The relevance of our findings for NASH pathogenesis was highlighted by the normalization of all of the changes 1 y after bariatric surgery. In conclusion, our data indicate that NAFL patients show changes in their immune cell profile compared with healthy controls. NAFL to NASH progression is marked by an increased frequency of IL-17+ cells among intrahepatic CD4+ T cells and higher Th17/rTreg and Th2/rTreg ratios in peripheral blood.
- Subjects :
- Adult
Male
0301 basic medicine
Pathology
medicine.medical_specialty
Regulatory T cell
Immunology
Bariatric Surgery
Biology
T-Lymphocytes, Regulatory
digestive system
Peripheral blood mononuclear cell
Gastroenterology
Pathogenesis
Interferon-gamma
Mice
03 medical and health sciences
Th2 Cells
Immune system
Non-alcoholic Fatty Liver Disease
Internal medicine
Nonalcoholic fatty liver disease
medicine
Animals
Humans
Immunology and Allergy
Lymphocyte Count
Prospective Studies
IL-2 receptor
Cells, Cultured
Interleukin-17
Fatty liver
nutritional and metabolic diseases
Middle Aged
medicine.disease
digestive system diseases
030104 developmental biology
medicine.anatomical_structure
Liver
Disease Progression
Th17 Cells
Female
Interleukin-4
Interleukin 17
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 196
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....2c1b6329aa565db2e395612ca1ca0bb1
- Full Text :
- https://doi.org/10.4049/jimmunol.1501175