Autoreactive memory Th17 cells are principally derived from T-bet⁺RORγt⁺ Th17/1 effectors

Area of Science:

• Immunology
• Autoimmunity research
• Cellular immunology

Background:

• Effector Th17 (T helper 17) cells, including IFN-γ-IL-17+ (eTh17) and IFN-γ+IL-17+ (eTh17/1) subsets, are implicated in autoimmune pathogenesis.
• Memory Th17 (mTh17) cells, derived from effector cells, are responsible for sustaining chronic inflammation in autoimmune conditions.

Purpose of the Study:

• To investigate the distinct roles of eTh17 and eTh17/1 cells in forming the memory Th17 cell pool.
• To elucidate the contribution of T-bet-dependent pathways in the differentiation of pathogenic memory Th17 cells.

Main Methods:

• Utilized an experimental model of ocular autoimmune disease.
• Employed adoptive transfer of Tbx21-deficient CD4+ T cells and Th17-specific Tbx21 conditional deletion.
• Analyzed the generation and function of effector and memory Th17 cell subsets during acute and chronic inflammatory phases.

Main Results:

• Diminished eTh17/1 cell populations and impaired mTh17 cell function were observed following Tbx21 deficiency.
• Adoptive transfer of disease-specific eTh17/1 cells, but not eTh17 cells, resulted in mTh17 cell generation and persistent ocular inflammation.
• T-bet-dependent eTh17/1 cells generated during acute inflammation are the primary precursors for pathogenic mTh17 cells.

Conclusions:

• T-bet-expressing eTh17/1 cells are critical for the development of pathogenic memory Th17 cells.
• These T-bet-dependent eTh17/1 cells are essential for sustaining chronic autoimmune inflammation, particularly in ocular disease models.