Dr. Sidong Xiong and Dr. Zhenke Wen have recently published their research article entitled “RORt licenses the differentiation and function of a unique subset of Tfh cells in response to immunogenic self-DNA in systemic lupus erythematosus” in Arthritis & Rheumatology, describing an essential function of RORt+ Tfh cells in immunogenic self-DNA-instructed auto-IgG generation and autoimmunity.
Systemic lupus erythematosus (SLE) is a devastating autoimmune disease that affects virtually any tissues and organs in young females. Immunogenic self-DNA drives IgG anti-dsDNA generation, serving as the major cause of lupus morbidity and mortality. However, mechanisms underpinning such auto-IgG generation are far less clear.
The findings in current study identify a refined understanding of the adaptive DNA immunity. Specifically, immunogenic self-DNA induces the differentiation and function of IL-17+ Tfh cells through RORt-dependent and ICOS-dispensable mechanisms. RORt acts as a key checkpoint for the differentiation and function of immunogenic self-DNA-specific Tfh cells, licensing IL-17 expression and IgG anti-dsDNA response. Targeting immunogenic self-DNA-specific Tfh cells via human RORknockdown and IL-17 neutralization restricts IgG anti-dsDNA response and lupus nephritis development in humanized lupus chimeras, providing relevant therapeutic strategies for lupus management in clinical practice.
Sidong Xiong, MD, PhD, and Zhenke Wen, MD, PhD, are the senior authors. The lead author is Dr. Zhenke Wen. Other co-authors are Dr. Lin Xu and Dr. Wei Xu. This work was supported by National Natural Science Foundation of China (81273300, 82071826), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Jiangsu Provincial Innovative Research Team and Project for Jiangsu Specially-Appointed Professor.