Vaccination-based immunotherapy to target profibrotic cells in liver and lung

Michal Sobecki, Jing Chen, Ewelina Krzywinska, Shunmugam Nagarajan, Zheng Fan, Eric Nelius, Josep M. Monné Rodriguez, Frauke Seehusen, Amro Hussein, Greta Moschini, Edries Y. Hajam, Ravi Kiran, Dagmar Gotthardt, Julien Debbache, Cécile Badoual, Tatsuyuki Sato, Takayuki Isagawa, Norihiko Takeda, Corinne Tanchot, Eric TartourAchim Weber, Sabine Werner, Johannes Loffing, Lukas Sommer, Veronika Sexl, Christian Münz, Carol Feghali-Bostwick, Elena Pachera, Oliver Distler, Jess Snedeker, Colin Jamora, Christian Stockmann

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Fibrosis is the final path of nearly every form of chronic disease, regardless of the pathogenesis. Upon chronic injury, activated, fibrogenic fibroblasts deposit excess extracellular matrix, and severe tissue fibrosis can occur in virtually any organ. However, antifibrotic therapies that target fibrogenic cells, while sparing homeostatic fibroblasts in healthy tissues, are limited. We tested whether specific immunization against endogenous proteins, strongly expressed in fibrogenic cells but highly restricted in quiescent fibroblasts, can elicit an antigen-specific cytotoxic T cell response to ameliorate organ fibrosis. In silico epitope prediction revealed that activation of the genes Adam12 and Gli1 in profibrotic cells and the resulting “self-peptides” can be exploited for T cell vaccines to ablate fibrogenic cells. We demonstrate the efficacy of a vaccination approach to mount CD8+ T cell responses that reduce fibroblasts and fibrosis in the liver and lungs in mice. These results provide proof of principle for vaccination-based immunotherapies to treat fibrosis.

Original languageEnglish
Pages (from-to)1459-1474.e9
JournalCell Stem Cell
Volume29
Issue number10
DOIs
StatePublished - 6 Oct 2022
Externally publishedYes

Keywords

  • activated fibroblasts
  • fibrogenic cells
  • immunotherapy
  • liver fibrosis
  • lung fibrosis
  • myofibroblasts
  • organ fibrosis
  • tissue regeneration
  • vaccination

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