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

Nai-Wen Fan; Shudan Wang; Gustavo Ortiz; Sunil K Chauhan; Yihe Chen; Reza Dana

doi:10.1016/j.jaut.2022.102816

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

J Autoimmun. 2022 May:129:102816. doi: 10.1016/j.jaut.2022.102816. Epub 2022 Apr 5.

Authors

Nai-Wen Fan¹, Shudan Wang², Gustavo Ortiz³, Sunil K Chauhan³, Yihe Chen⁴, Reza Dana⁵

Affiliations

¹ Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA; Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, 11217, Taiwan; Faculty of Medicine, National Yang Ming Chiao Tung University, Hsinchu, 30010, Taiwan.
² Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA; Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
³ Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA.
⁴ Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA. Electronic address: yihe_chen@meei.harvard.edu.
⁵ Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA. Electronic address: reza_dana@meei.harvard.edu.

Abstract

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.

Keywords: Effector Th17/1; Memory Th17; T-bet.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Autoimmune Diseases* / pathology
Humans
Inflammation / pathology
Interferon-gamma
Interleukin-17 / genetics
Nuclear Receptor Subfamily 1, Group F, Member 3*
Th1 Cells
Th17 Cells

Substances

Interleukin-17
Nuclear Receptor Subfamily 1, Group F, Member 3
Interferon-gamma

Abstract

Publication types

MeSH terms

Substances

Grants and funding