Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease (IBD) that results in recurrent inflammation and ulcers of the colon and rectum, and it is a risk factor for colitis-associated colon cancer (CAC) [1]. The incidence of IBD is increasing worldwide, especially in the developing countries [2]. Currently, the World Health Organization (WHO) has classified UC as a contemporary form of refractory illness, for which the existing treatment options have not yet provided a complete cure [3,4]. Growing evidence indicate that memory regulatory T cells (mTreg) play a crucial role in the development of IBD, making it a highly researched area [5,6]. Therefore, modulating both immunometabolic and immune memory could be an important therapeutic modality for UC [7,8].

Regulatory T cells (Tregs), a subset of T cells, have the ability to suppress immune responses and are crucial in maintaining immune homeostasis [9]. mTreg refers to a group of T cells that possess both immune memory and inhibitory capabilities. A significant amount of evidence has confirmed that after the initial inflammatory response has been suppressed and eliminated, when the body is stimulated by the same antigen again, the immune memory will be activated, and the mTregs will be activated again. By selectively inhibiting the immune system's capacity to generate an excessively robust immune response to secondary antigens and enhancing the body's immune tolerance, Treg cells effectively hinder the recurrence of disease [10]. However, the body encounters a secondary antigenic stimulus when an inferior level and function of mTreg cells, the inability of mTreg cells to rapidly transform into effector Treg cells to play the role of immune tolerance leads to uncontrolled autoimmune responses, decreased immune tolerance of the intestinal mucosa, persistent inflammatory injury, and the induction of intestinal autoimmune diseases, including inflammatory bowel disease [11]. Some researchers directly engrafted mTreg cells into UC mice, demonstrating promising therapeutic effects [12]. Therefore, improving immune metabolism to regulate the level of immune memory is 1 of the important strategies for the treatment of IBD.

Astragalus membranaceus, a traditional Chinese herb, contains Astragalus polysaccharides (APS) as a key active ingredient. APS exhibits various pharmacological effects including anti-inflammatory, immunoregulatory, antiviral, hypoglycemic, antioxidant, hepatoprotective, and anti-tumor properties [13,14]. Many clinical studies have indicated that APS can effectively treat colotis in both animals and humans by ameliorating inflammation, modulating signal transduction, regulating the immune system, balancing intestinal flora, and protecting intestinal mucosal barrier, etc. [15,16]. The previous studies have shown that APS has the potential to enhance ulcerative colitis in mice by effectively controlling T lymphocytes, increasing the levels of Treg cells, maintaining a balanced ratio of Tfh/Treg cells, and suppressing the production of inflammatory factors [17,18]. Nevertheless, the precise impact and mechanism of APS on mTreg cells in the treatment of UC remain uncertain. Hence, in order to explore the potential mechanism of APS in the treatment of DSS-induced colitis, we utilized flow cytometry to observe the altered characteristics of Treg and mTreg cells and employed transcriptomic sequencing to investigate the pathway of APS alleviated UC.