Yi-Qi-Jian-Pi formula ameliorates immune function in acute-on-chronic liver failure by upregulating autophagy and mitochondrial biogenesis in CD8 T lymphocytes.

ETHNOPHARMACOLOGICAL RELEVANCE

A key event in the pathogenesis of acute-on-chronic liver failure (ACLF) is the imbalance in the systemic immune response; immunosuppression in patients with ACLF contributes to poor prognosis. The Yi-Qi-Jian-Pi formula (YQJPF) may improve T lymphocyte immune function in patients with ACLF.

AIM OF THE STUDY

To investigate the immune mechanism of YQJPF in vivo and in vitro.

MATERIALS AND METHODS

An ACLF rat model was established by injection of CCl, lipopolysaccharide, and D-galactosamine. We examined the effect of different doses of YQJPF (6.43, 12.87, 25.74 g/kg) on liver injury and immune function in the ACLF rat model. Magnetic-activated cell sorting was used to sort the CD8 T lymphocytes in the spleen for lymphocyte function detection. In primary CD8 T lymphocytes and Jurkat cell lines, the expression of mitochondrial function and biogenesis and autophagy related markers were detected using molecular biological methods and flow cytometry analysis.

RESULTS

YQJPF improved the peripheral blood lymphocyte count and proportion of CD8 T lymphocytes in ACLF rats, increased pro-inflammatory factors (IL-2, IFN-λ, and TNF-α), and reduced anti-inflammatory factors (IL-10 and TGF β1). YQJPF also improved metabolism and mitochondrial homeostasis in CD8 T lymphocytes, alleviated lymphocyte immune dysfunction by promoting autophagy, upregulated mitochondrial biogenesis by promoting PGC-1α, NRF-1, and TFAM expression, and regulated the relationship between autophagy and mitochondrial biogenesis via PGC-1α.

CONCLUSIONS

Our results suggest that YQJPF could improve immune function in a rat model of ACLF, possibly via affecting the homeostasis of lymphatic mitochondria in CD8 T lymphocytes. YQJPF may enhance lymphocyte mitochondrial biosynthesis and promote lymphocyte autophagy. PGC-1α is a possible upstream regulatory target of YQJPF.