TLR2 Supports γδ T cell IL-17A Response to ocular surface commensals by Metabolic Reprogramming

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• The ocular surface hosts microbes that modulate local immunity.
• Commensal bacteria, like *Corynebacterium mastitidis*, induce protective IL-17 responses from conjunctival T cells.

Purpose of the Study:

• To identify novel microbial-responsive T cell subsets in the conjunctiva.
• To elucidate the unique activation requirements of Vγ6 T cells in response to *C. mastitidis*.

Main Methods:

• Flow cytometry and cytokine analysis to characterize T cell responses.
• Gene expression and epigenetic analysis to understand molecular mechanisms.
• Mice models to study *in vivo* immune responses.

Main Results:

• Vγ6 T cells were identified as a major subset responding to *C. mastitidis*.
• Optimal IL-17A production by Vγ6 cells requires both extrinsic (dendritic cell) and intrinsic TLR2 stimulation.
• Intrinsic TLR2 signaling induces epigenetic modifications and a metabolic shift towards fatty acid oxidation, supporting IL-17A transcription.
• IκBζ was identified as a key transcription factor upregulated by TLR2, essential for this process.

Conclusions:

• Intrinsic TLR2 signaling is critical for Vγ6 T cell function.
• Microbiome-induced metabolic reprogramming in T cells supports IL-17A production.
• This study reveals a novel mechanism of mucosal immunity mediated by specific γδ T cells.