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. 2025 Sep;398(9):12585-12598.
doi: 10.1007/s00210-025-04089-9. Epub 2025 Apr 3.

Investigating the therapeutic potential of tryptophan and vitamin A in modulating immune responses in celiac disease: an experimental study

Fatemeh Asgari  1   2 , Abdolrahim Nikzamir  3 , Kaveh Baghaei  4 , Andrea Masotti  5 , Mohammad Rostami-Nejad  6
Affiliations

Investigating the therapeutic potential of tryptophan and vitamin A in modulating immune responses in celiac disease: an experimental study

Fatemeh Asgari et al. Naunyn Schmiedebergs Arch Pharmacol. 2025 Sep.

Abstract

Dendritic cells (DCs) play a crucial role in gliadin-induced inflammation in celiac disease as they are the first immune cells to encounter gliadin. Tryptophan (Trp) and vitamin A (retinol, Ret) are known to influence the immune response of DCs to gliadin and increase their tolerogenicity. CD4 + CD25 + Foxp3 + regulatory T cells (Tregs), which are important for immune tolerance, can be generated from naive T cells in the presence of retinoic acid (RA) and TGF-β.The aim of this study was to determine the combined effect of Ret and Trp in altering the phenotypic and functional maturation of DCs by gliadin and their contribution to the differentiation of Tregs. Monocyte cells derived from the peripheral blood mononuclear cells (PBMCs) of patients with celiac disease were differentiated into DCs and stimulated with PT-gliadin. These cells were then treated with Trp + Ret. The expression of CD11c, CD14, CD83, CD86, PDL1, CD4, CD25 and FOXP3 was examined using flow cytometry. TGF-β, IL-10, IL-12, and TNF-α levels were measured by ELISA. qRT-PCR was used to quantify the mRNA levels of retinaldehyde dehydrogenase 2 (RALDH2), integrin αE (CD103), and NF-κB. Indoleamine 2,3-dioxygenase (IDO) mRNA and protein levels were assessed using qRT-PCR and Western blot assays, respectively. The maturation of DCs by PT-gliadin was defined through co-stimulatory molecule expression (CD83 and CD86) and promotion of TNF-α and IL-12 secretion. We found that after treatment with Ret + Trp, the production levels of IL-12, TNF-α, and NF-κB were significantly reduced, while the expression of IL-10, TGF-β, and the inhibitory markers PDL1, CD103, IDO, and RALDH2 by PT-gliadin-stimulated DCs was significantly increased. Furthermore, in a DC and T cell co-culture system, treatment of DCs with Ret + Trp increased TGF-β expression in DCS and promoted CD4 + CD25 + FOXP3 Treg induction. These results indicate the potential benefit of vitamin A and tryptophan as therapeutic options for individuals with celiac disease. Further research is required to fully understand the mechanisms of action of these substances in these cells.

Keywords: Celiac disease; Dendritic cells; Immune tolerance; Retinol; T regulatory; Tryptophan.

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Conflict of interest statement

Declarations. Ethical considerations: The protocols for the current project were reviewed and approved by the ethics committees of the Shahid Beheshti University of Medical Sciences (SBMU) before the research could begin (Code of Ethics: IR. SBMU. RETECH. REC.1403.382) and Clinical trial number: not applicable. Each participant signed written informed consent before sampling. Conflict of interest: The authors declare no competing interests.

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