2. Academic Validation
  3. Exogenous dendritic cell-derived exosomes promote Treg differentiation via IDO1-Kyn-AhR axis and improve cardiac function after myocardial infarction

Exogenous dendritic cell-derived exosomes promote Treg differentiation via IDO1-Kyn-AhR axis and improve cardiac function after myocardial infarction

  • Int Immunopharmacol. 2026 Mar 15:173:116253. doi: 10.1016/j.intimp.2026.116253.
Yiran Qin 1,  Youming Zhang 2,  Mingxuan Li 3,  Di Ding 1,  Rong Luo 4,  Haibo Liu 5
Affiliations

Affiliations

  • 1 Department of Cardiology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, China.
  • 2 Department of Cardiology, Shanghai East Hospital, Tongji University, Shanghai 200120, China.
  • 3 Department of Cardiology, Huadong Hospital, Fudan University, Shanghai 200040, China.
  • 4 Department of Cardiology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, China. Electronic address: [email protected].
  • 5 Department of Cardiology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, China. Electronic address: [email protected].
PMID: 41581242 DOI: 10.1016/j.intimp.2026.116253
Abstract

Regulatory T cells (Tregs) play a vital role in cardiac remodeling after myocardial infarction (MI). Our previous study demonstrated that dendritic cell-derived exosomes (DEXs) improve cardiac function after MI by promoting Treg differentiation. However, the underlying mechanisms remain incompletely understood. In this study, we found that necrotic HL-1 cardiomyocyte supernatant-conditioned DEXs (MI-DEXs) expressed high level of indoleamine 2,3-dioxygenase 1 (IDO1), which led to increased kynurenine (Kyn) production and subsequently upregulation of Aryl Hydrocarbon Receptor (AhR) in CD4+ T cells. Overexpression of IDO1 in MI-DEXs enhanced Treg differentiation and further improved cardiac function after MI, whereas knockdown of IDO1 attenuated these effects. In addition, pharmacological inhibition of AhR abolished the enhanced Treg differentiation and functional benefits induced by IDO1-overexpressing MI-DEXs, both in vitro and in vivo. Collectively, our findings reveal a novel mechanism by which MI-DEXs promote Treg differentiation via the IDO1-Kyn-AhR axis, and suggest that administration of MI-DEXs could be a potential intervention to facilitate cardiac repair after MI.

Keywords

Dendritic cells; Exosomes; Indoleamine 2,3-dioxygenase 1; Myocardial infarction; Regulatory T cells.

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