# Heat-killed Lactobacillus johnsonii Directly Inhibits Th17 Cell Effector Function via Selective Translational Suppression

## TL;DR

Heat-killed Lactobacillus johnsonii suppresses IL-17A production in Th17 cells without killing them, offering a new way to control inflammation.

## Contribution

HK Lj selectively inhibits IL-17A translation in Th17 cells, independent of antigen-presenting cells or receptor signaling.

## Key findings

- HK Lj directly suppresses IL-17A production in iTh17 cells without affecting their viability.
- The suppression occurs at the translational level without altering mRNA or other cytokines.
- The mechanism is independent of Toll-like or C-type lectin receptor signaling.

## Abstract

Interleukin-17A (IL-17A)–producing Th17 cells are essential for mucosal host defense but also drive chronic inflammation and fibrosis when dysregulated. While commensal Lactobacillus species modulate Th17 responses through antigen-presenting cells, their direct effects on differentiated Th17 cells are poorly understood. We demonstrate that heat-killed Lactobacillus johnsonii XZ17 (HK Lj) directly suppresses IL-17A production in induced Th17 (iTh17) cells, independent of antigen-presenting cells. Unlike live L. johnsonii, which reduces IL-17A via environmental acidification and cell death, HK Lj preserves iTh17 viability. Mechanistically, HK Lj selectively inhibits IL-17A translation without altering II17a or Rorc mRNA levels, global protein synthesis, or other cytokines like IL-10. This suppression is independent of Toll-like or C-type lectin receptor signaling. These findings reveal a previously unrecognized mechanism by which a commensal-derived stimulus directly regulates cytokine translation, positioning HK Lj as a potential immunomodulatory agent for targeting pathological IL-17A while maintaining T cell survival.