Bridging pDCs and cDCs: The Identity of Transitional Dendritic Cells

Area of Science:

• Immunology
• Cell Biology

Background:

• Transitional dendritic cells (tDCs) represent a hybrid subset bridging plasmacytoid (pDC) and conventional dendritic cell (cDC) lineages.
• tDCs possess unique effector functions, distinct from both pDCs and cDC2s, including IL-1β production and antigen presentation.

Purpose of the Study:

• To review current insights into transitional dendritic cell (tDC) biology, including their origin, development, and immune function.
• To highlight the dynamic spectrum of tDC states and their implications for understanding immune responses.

Main Methods:

• Synthesis of current literature on tDC biology across species.
• Analysis of high-dimensional single-cell profiling data identifying tDC characteristics.

Main Results:

• tDCs are ontogenetically related to pDCs but do not produce type I interferon; instead, they rapidly initiate innate inflammation via IL-1β.
• tDCs exhibit antigen capture and CD4+ T cell priming capabilities similar to cDC2s.
• tDCs exist along a differentiation continuum (tDClo, tDChi, CD11b- tDC2s, tDC-derived DC2s), indicating plasticity in DC identity.

Conclusions:

• tDCs challenge the rigid pDC/cDC dichotomy, demonstrating that DC identity is temporally programmed and plastic.
• Understanding tDC plasticity offers potential therapeutic avenues for infection, cancer, and autoimmunity.