Hepatic stellate cells attenuate the immune response in renal transplant recipients with chronic hepatitis

Background

Chronic viral hepatitis is no longer a contraindication to renal transplantation (RT), owing to our better understanding of the hepatitis virus. Hepatitis patients may receive RT depending on their response to viral therapy. RT patients with hepatitis generally do not have an inferior prognosis compared with RT patients without the disease. Hepatic stellate cells (HSCs) are activated during chronic viral hepatitis. The role of HSCs in immunoregulatory effects in RT recipients has not been fully elucidated.

Methods

We recruited 22 RT recipients with chronic viral hepatitis, who composed the chronic liver disease (CLD) group, and 25 disease-free recipients, who served as the control group. We retrieved their clinical data and collected serum to measure cytokine levels. To investigate the immunoregulatory effect of HSCs, we cocultured HSCs with allogeneic antigen-presenting cell-activated T cells (mixed lymphocyte reaction [MLR]) in Transwell plates.

Results

The liver biopsy disclosed activation HSCs in 1 chronic hepatitis C virus recipient without treatment. Serum monocyte chemoattractant protein-1 (MCP-1) levels in the CLD group (41.6 ± 27.4 pg/mL) were significantly higher than those in the control group (28.1 ± 12.8 pg/mL; P = .008). There were similar levels of transforming growth factor-β1 (TGF-β1). In allogeneic MLR, HSCs inhibited T-cell activation through the soluble factors in the Transwell assays. There was a high level of MCP-1 in the supernates of the HSC group in the allogeneic MLR, but TGF-β1 was lower in HSCs cocultured with MLR than in the control group, except in the early period.

Conclusions

HSCs may play an immunoregulatory role in chronic viral hepatitis recipients to minimize the effect of immunosuppressants without affecting rejection. The immunomodulatory effects may be attributed to soluble factors in HSCs.