Background: Mucosal-associated invariant T (MAIT) cells comprise a subpopulation of T cells that can be activated by bacterial products and cytokines to produce IFN-γ. Little is known about the role of MAIT cells in fibrosis progressions in fatty liver disease. Aim: To assess frequency and phenotype of MAIT cells with correlation of liver fibrosis severities in NAFLD patients.

Methods: Age, BMI, ALT, serum-fasting-insulin levels, HbA1c, HOMA-IR score, TG, HDL, LDL and CRP were correlated with histological outcome (%steatosis, necro-inflammatory activity, fibrosis-scoring) in adult NAFLD cases lacking metabolic-syndrome or other liver etiologies. In-vitro, peripheral blood obtained from healthy donors (n=7) and NAFLD patients (n=22, of them 20 with steatohepatitis). Using flow cytometry we identified MAIT cells by the expression of CD3, CD161 and TCR Vα7.2. For immune phenotyping we used markers like TNFa, CD69, CD38 and IL17.

Results: 22-cases fulfill inclusion/exclusion criteria, all are males, mean age at biopsy 39.4±10.6y, BMI 29±2.8. Seven had cirrhosis as scores were F4. Serum HOMA-IR found the most significant predictor for histological severity. Lower serum insulin levels significantly correlated with decreased hepatic-fat-content but increased liver-injury (fibrosis-scoring & necro-inflammatory-activity), IR (serum insulin levels, HbA1c & HOMA-IR score). Healthy donors had 12.68%±1.11 MAIT cells and were significantly decreased in peripheral blood of patients with NAFLD to 10.62%±1.37, 3.9%±0.71, 1.66%±0.08 and 1.2%±0.21 with fibrosis grades of F1, F2, F3 and F4, respectively.  Moreover, MAIT cells from patients showed higher expression of activation and exhaustion markers such as CD69 and CD38, respectively as compared to heathy donors. MAIT cells had also elevated IL-17 expression, a pro-fibrogenic cytokine as well as TNFa, a pro-inflammatory cytokine. These results were linearly correlated with fibrosis severities. The frequency of MAIT cells was negative correlation with HOMA-IR score (r=-0.33, p=0.02). Conclusion: Decreased expressions of peripheral blood MAIT cells in NAFLD patients were inversely correlated with the fibrosis stage. These results were associated with MAIT cells exhaustions and increased their TNFa and IL17 productions. Our data suggest MAIT cells might contribute to the development of fibrosis in NAFLD and represent a novel therapeutic target.

Conference Title

EASL-Paris

Conference Country

Palestine

Conference Date

April 11, 2018 - April 15, 2018

Conference Sponsor

EASL

Additional Info

Conference Website