BATF regulates Treg-cell functional specification and fitness of triglyceride metabolism in restraining allergic responses

• Published in: The Journal of immunology (1950) 2021-04, Vol.206 (9), p.2088-2100
• Main Authors: Xu, Chengxian, Fu, Yongyao, Liu, Sheng, Trittipo, Jack, Lu, Xiaoyu, Qi, Rong, Du, Hong, Yan, Cong, Zhang, Chi, Wan, Jun, Kaplan, Mark H., Yang, Kai
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.2001184

Preserving appropriate function and metabolism in Treg cells is crucial for controlling immune tolerance and inflammatory responses. Yet how Treg cells coordinate cellular metabolic programs to support their functional specification remains elusive. Here we report that BATF couples the T H 2 suppressive function and triglyceride (TG) metabolism in Treg cells for controlling allergic airway inflammation and IgE responses. Mice with Treg-specific ablation of BATF developed an inflammatory disorder characterized by T H 2-type dominant responses, and were predisposed to house dust mite (HDM)-induced airway inflammation. Loss of BATF enabled Treg cells to acquire T H 2-cell-like characteristics. Moreover, BATF-deficient Treg cells displayed elevated levels of cellular TGs, and repressing or elevating TGs respectively restored or exacerbated their defects. Mechanistically, T cell receptor (TCR)/CD28 co-stimulation enhanced expression and function of BATF, which sustained IRF4 activity to preserve Treg cell functionality. Thus, our studies reveal that BATF links Treg cell functional specification and fitness of cellular TGs to control allergic responses, and suggest that therapeutic targeting of TG metabolism could be used for the treatment of allergic disease.