Mechanism of recombinant Trichinella spiralis antigen p53 alleviating experimental colitis via the IDO-AhR Axis

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder characterized by disrupted intestinal immune homeostasis. Emerging evidence indicates that parasitic infections may exert anti-inflammatory effects by modulating host immunity, although the underlying molecular mechanisms remain incompletely elucidated. This study aimed to investigate whether recombinant Trichinella spiralis (T. spiralis) antigen p53 (rTs p53) protects against experimental colitis by regulating the indoleamine 2, 3-dioxygenase (IDO)-aryl hydrocarbon receptor (AhR) axis.

In vitro assays were performed to evaluate the effects of rTs p53 on IDO expression in dendritic cells (DCs), the kynurenine/tryptophan (Kyn/Trp) ratio, cytokine secretion, and regulatory T cell (Treg) frequency. Specific inhibitors were used to functionally validate the IDO and AhR pathways. In a dextran sulfate sodium (DSS)-induced mouse model of chronic colitis, the therapeutic efficacy of rTs p53 was assessed comprehensively using the disease activity index, colon length, histopathological scoring, myeloperoxidase (MPO) activity, cytokine levels, and flow cytometric analysis of immune cell populations. Mechanistic validation was further conducted in vivo and in vitro by combined administration of the IDO inhibitor 1-MT and the AhR antagonist CH-223191.

In vitro, rTs p53 stimulation significantly upregulated IDO expression in DCs, elevated the Kyn/Trp ratio, promoted CD4⁺ T cell differentiation into Tregs, and suppressed Th17 polarization through activation of the AhR pathway. These effects were abrogated by the IDO inhibitor 1-MT or the AhR antagonist CH-223191. In mice with DSS-induced colitis, rTs p53 treatment markedly ameliorated disease activity, alleviated colonic histopathological damage, downregulated proinflammatory cytokine levels, and restored the Treg/Th17 balance. Notably, co-administration of 1-MT or CH-223191 significantly attenuated these protective effects.

This study demonstrates that rTs p53 promotes Trp catabolism toward Kyn by activating the IDO-AhR signaling axis in DCs. This mechanism regulates the Treg/Th17 balance, suppresses intestinal inflammatory responses, and ultimately mitigates experimental colitis. These findings provide a novel perspective for clarifying the mechanisms of parasite-derived immunomodulatory molecules and offer experimental evidence for the development of IDO-AhR-targeted therapeutic strategies against IBD.