Inside Job: Cholangiocyte-T Cell Interactions and Immunomodulation in PBC

Primary Biliary Cholangitis (PBC) is a cholestatic liver disease characterized by a distinctive immune-mediated pathogenesis. Central to biliary damage is the intricate crosstalk between T cells and biliary epithelial cells (BECs), the latter of which have emerged as active participants rather than passive targets in disease development. An aberrant phenotype exhibited by these epithelial cells has indeed been proposed as a key driver of damage. Recently, our laboratory uncovered a novel pathogenic interaction whereby activated T cells invade dysfunctional BECs, a phenomenon we have termed AVentosis. This mechanism illustrates how autoimmune responses can link epithelial damage to sustained chronic inflammation in PBC.

In the second part of this presentation, I will discuss a promising immunomodulatory platform as a potential therapeutic strategy for PBC, leveraging its status as a prototypical autoimmune disease with a clearly defined antigenic target.

Finally, the talk will briefly outline a unifying hypothesis integrating autoimmune and epithelial-secretory dysfunction theories, potentially applicable not only to PBC but also to other immune-mediated epithelial disorders.