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

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Th17 cells and their cytokine Interleukin-17A (IL-17A) are crucial for host defense but implicated in chronic inflammatory diseases.
• Commensal Lactobacillus species are known to modulate immune responses, but their direct impact on differentiated Th17 cells remains unclear.

Purpose of the Study:

• To investigate the direct effects of heat-killed Lactobacillus johnsonii XZ17 (HK Lj) on IL-17A production by Th17 cells.
• To elucidate the underlying molecular mechanisms of this interaction, independent of antigen-presenting cells.

Main Methods:

• In vitro culture of induced Th17 (iTh17) cells with HK Lj.
• Analysis of IL-17A production, cell viability, mRNA levels (Il17a, Rorc), global protein synthesis, and other cytokine expression (IL-10).
• Assessment of Toll-like and C-type lectin receptor involvement.

Main Results:

• HK Lj directly suppressed IL-17A production in iTh17 cells without affecting cell viability.
• Suppression occurred at the translational level, without altering Il17a mRNA levels or global protein synthesis.
• The effect was independent of antigen-presenting cells and Toll-like/C-type lectin receptor signaling.

Conclusions:

• Heat-killed Lactobacillus johnsonii XZ17 directly inhibits IL-17A translation in Th17 cells, representing a novel immunomodulatory mechanism.
• This commensal-derived stimulus selectively targets pathological IL-17A production while maintaining T cell survival, suggesting potential therapeutic applications.