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July 19, 2026Biomedicine & PharmacotherapyOpen Access

TGR5 activation impairs lung natural killer cell function and promotes bile acid–mediated injury in metabolic liver disease

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Authors

AFAlaa Mohammed FelelMJMohammad JaberHTHanin Takhman

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Overview

Randomized trial shows TGR5 activates to impair NK cell function in metabolic liver disease, suggesting new treatment paths.

Key Points

  • The study aims to understand how elevated bile acids influence natural killer cell function and lung injury in metabolic liver disease.
  • Leptin-deficient mice were fed a high-fat diet for 16 weeks to induce metabolic liver disease.
  • Flow cytometry analyzed NK cell activation and TGR5 expression, while lung injury markers were quantified from bronchoalveolar lavage fluid.
  • Ex-vivo assays assessed the impact of taurocholic acid and TGR5 blockade on NK cell activation.
  • Ob/Ob mice developed metabolic liver disease with significant lung injury, showing lung weight increased by ∼1.5 g compared to controls.
  • SP-D and sRAGE levels increased 2.5-fold and 2.0-fold, respectively (P < 0.01), indicating severe lung injury.
  • NK cell activity was reduced by 3.5-fold, while TGR5 expression on NK cells increased ∼3.5-fold, suggesting a detrimental role of TGR5 signaling.

Cite This Study

Felel et al. (2026) studied this question.

synapsesocial.com/papers/6a5c69c3118b92953e3ee03dhttps://doi.org/10.1016/j.biopha.2026.119732
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