Nucleic acid sensing by T cells initiates Th2 cell differentiation

Area of Science:

• Immunology
• Molecular Biology
• Cellular Biology

Background:

• Toll-like receptor (TLR) ligands modulate T-cell responses.
• The role of nucleic acids (NAs) in T-cell costimulation is not fully understood.

Purpose of the Study:

• To investigate the mechanism and physiological function of NA-mediated T-cell costimulation.
• To elucidate the role of NA sensing in T cells for immune responses, particularly allergic inflammation.

Main Methods:

• T cells were exposed to various NA complexes, including self-DNA complexed with antimicrobial peptides or histones.
• Costimulatory responses were assessed independently of known NA sensors like TLRs, RLRs, inflammasomes, and STING.
• T-cell differentiation and cytokine production were analyzed, focusing on Th2 responses.

Main Results:

• T cells exhibit costimulatory responses to non-CpG DNA and self-DNA complexes, independent of canonical NA sensors.
• NA internalization by T cells triggers costimulation.
• NA-mediated costimulation suppresses T-bet expression, inducing GATA-3 and Th2 cytokines, crucial for Th2 differentiation.

Conclusions:

• T cells possess intrinsic NA sensing pathways that mediate costimulation.
• This NA sensing by T cells is critical for inducing Th2 differentiation and amplifying allergic inflammation.
• These findings uncover a novel function of NA sensing in T cells, linking innate-like sensing to adaptive immune polarization.