biostudies-literatureFan NWNEI NIH HHS102816https://www.ebi.ac.uk/biostudies/studies/S-EPMC9106930biostudies-literatureUnknown129Effector Th17 cells, including IFN-γ^-IL-17⁺ (eTh17) and IFN-γ⁺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 diseases. 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 functionally 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.Journal of autoimmunityAutoreactive memory Th17 cells are principally derived from T-bet⁺RORγt⁺ Th17/1 effectors.PMC9106930P30 EY003790R01 EY020889Ortiz GDana RWang SFan NWChen YChauhan SKfalseAutoreactive memory Th17 cells are principally derived from T-bet⁺RORγt⁺ Th17/1 effectors.Effector Th17 cells, including IFN-γ^-IL-17⁺ (eTh17) and IFN-γ⁺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 diseases. 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 functionally 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.2022-01-01T00:00:00Z2022 May2025-04-19T13:31:09.561Z2025-04-19T13:31:09.561ZS-EPMC91069303539554110.1016/j.jaut.2022.102816