Autoreactive memory Th17 cells are principally derived from T-bet+ROR?t+ Th17/1 effectors

Effector Th17 cells, including IFN-gamma-IL-17(+) (eTh17) and IFN-gamma+IL-17(+ )(eTh17/1) subsets, play critical pathogenic functions in the induction of autoimmunity. As acute inflammation subsides, a small proportion of the effectors survive and convert to memory Th17 cells (mTh17), which sustain chronic inflammation in autoimmune dis-eases. Herein, we investigated the differential contributions of eTh17 versus eTh17/1 to the memory pool using an experimental model of ocular autoimmune disease. Our results show that adoptive transfer of Tbx21-/- CD4+ T cells or conditional deletion of Tbx21 in Th17 cells leads to diminished eTh17/1 in acute phase and func-tionally compromised mTh17 in chronic phase. Further, adoptive transfer of disease-specific eTh17/1, but not eTh17, leads to generation of mTh17 and sustained ocular inflammation. Collectively, our data demonstrate that T-bet-dependent eTh17/1 cells generated during the acute inflammation are the principal effector precursors of pathogenic mTh17 cells that sustain the chronicity of autoimmune inflammation.

Automated summary

This study reveals the important role and transformation process of Th17 cells in autoimmune diseases. During the acute phase, eTh17/1 cells are the principal effector precursor cells, while mTh17 cells play a critical role in the chronic phase.