Single-cell transcriptomic profiling reveals diversity in human iNKT cells across hematologic tissues.

Area of Science:

• Immunology
• Cell Biology
• Genomics

Background:

• Invariant natural killer T (iNKT) cells are crucial innate lymphocytes with roles in immunity and potential therapeutic applications.
• Understanding human iNKT cell heterogeneity is limited, despite known mouse subset diversity.

Purpose of the Study:

• To delineate the transcriptomic diversity of human iNKT cells across various hematologic tissues.
• To identify novel transcriptional profiles and transcription factor dynamics in human iNKT cells.

Main Methods:

• Transcriptomic analysis of human iNKT cells from multiple immunologically relevant tissues.
• Comparative analysis with existing mouse iNKT cell data.

Main Results:

• Human iNKT cells exhibit naive/precursor, transitional, and T helper (Th)1/17/NK-like transcriptional profiles.
• Novel transcription factor dynamics and a T effector memory RA+ population were identified.
• Two distinct CD8+ iNKT cell patterns were observed, one naive/precursor-like and another Th1/17/NK-like.

Conclusions:

• Human iNKT cell heterogeneity is complex and partially distinct from mouse models.
• These findings provide critical insights for future functional studies and iNKT-based cellular therapy development.