TCF1-LEF1 co-expression identifies a multipotent progenitor cell (T_H2-MPP) across human allergic diseases.

Area of Science:

• Immunology
• Cell Biology

Background:

• Chronic infections and cancer lead to T cell exhaustion, impairing adaptive immunity.
• Allergic diseases exhibit aberrant, long-lasting T cell responses.
• Understanding divergent T cell fates is crucial for immune regulation.

Purpose of the Study:

• To investigate the mechanisms behind sustained T cell responses in human allergic disease.
• To identify novel T cell populations involved in chronic inflammation.

Main Methods:

• Bioinformatic analysis
• Immunophenotyping of human diseased tissues
• Functional assays
• Single-cell T-cell-receptor lineage tracing

Main Results:

• Identified abundant type 2 helper T (T_H2) cells co-expressing TCF7 and LEF1, termed T_H2-multipotent progenitors (T_H2-MPP).
• T_H2-MPP cells self-renew and differentiate into effector T_H2, regulatory T (T_reg), and follicular helper T (T_FH) cells.
• T_H2-MPP cells persisted despite IL-4 receptor blockade and were expanded by thymic stromal lymphopoietin (TSLP), gaining resistance to apoptosis.

Conclusions:

• T_H2-MPP cells are a distinct progenitor population driving chronic type 2 inflammation.
• These cells coordinate sustained T cell responses over time in allergic diseases.
• Identifies a potential therapeutic target for managing chronic allergic inflammation.