한빛사 논문
Chan Johng Kim,1,2 Choong-Gu Lee,1 Ju-Yang Jung,3 Ambarnil Ghosh,1 Syed Nurul Hasan,1,2 Sung-Min Hwang,1,2 Hyeji Kang,1 Changhon Lee,1,2 Gi-Cheon Kim,1 Dipayan Rudra,1 Chang-Hee Suh,3 and Sin-Hyeog Im 1,2,4,*
1 Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Gyeongbuk 37673, Republic of Korea
2 Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, Republic of Korea
3 Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do 16499, Republic of Korea
4 Lead Contact
*Correspondence : Sin-Hyeog Im
Abstract
Single-nucleotide polymorphisms in ETS1 are associated with systemic lupus erythematosus (SLE). Ets1-/- mice develop SLE-like symptoms, suggesting that dysregulation of this transcription factor is important to the onset or progression of SLE. We used conditional deletion approaches to examine the impact of Ets1 expression in different immune cell types. Ets1 deletion on CD4+ T cells, but not B cells or dendritic cells, resulted in the SLE autoimmunity, and this was associated with the spontaneous expansion of T follicular helper type 2 (Tfh2) cells. Ets1-/- Tfh2 cells exhibited increased expression of GATA-3 and interleukin-4 (IL-4), which induced IgE isotype switching in B cells. Neutralization of IL-4 reduced Tfh2 cell frequencies and ameliorated disease parameters. Mechanistically, Ets1 suppressed signature Tfh and Th2 cell genes, including Cxcr5, Bcl6, and Il4ra, thus curbing the terminal Tfh2 cell differentiation process. Tfh2 cell frequencies in SLE patients correlated with disease parameters, providing evidence for the relevance of these findings to human disease.
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