Journal
CELL AND BIOSCIENCE
Volume 12, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13578-022-00780-z
Keywords
Aryl hydrocarbon receptor; Crohn's disease; Dendritic cells; Intestinal immune tolerance; Treg cells
Categories
Funding
- National Natural Science Foundation of China [81770553, 82070568]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [JX10213640]
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This study found that activation of AhR in DCs can induce tolerogenic DCs, promote Treg cell differentiation, and alleviate the severity of intestinal inflammation. Transplanted tolDCs can also maintain the balance of Th17/Treg differentiation. Therefore, AhR may be a potential therapeutic target for CD.
Background Intestinal immune dysfunction is involved in the onset of Crohn's disease (CD). Dendritic cells (DCs), antigen-presenting cells, play a key role in the maintenance of intestinal immune homeostasis. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor widely expressed in various immune cells, including DCs. Although AhR plays an important role in immune tolerance, its role in the DCs is unclear. The purpose of this study was to investigate whether the activation of AhR can induce tolerogenic DCs (tolDCs) and the differentiation of regulatory T (Treg) cells, as well as ameliorate experimental colitis. Results AhR activation in the DCs resulted in a lower expression of surface markers such as CD80, CD83, CD86, and pro-inflammatory cytokine production, and higher anti-inflammatory production (IL-1 beta, IL-23, and IL-12) compared to the control DCs. The surface dendrites in DCs were significantly reduced following AhR activation by 6-formylindolo [3,2-b]carbazole (FICZ). Such DCs with FICZ-mediated activation of AhR, namely tolDCs, promoted Treg cell differentiation. Adoptive transfer of tolDCs to a TNBS-induced colitis mouse model significantly alleviated the severity of inflammation by improving the colon length and decreasing the disease activity index (DAI) and histopathological score. Moreover, the transferred tolDCs decreased the frequency of Th17 cells and increased the frequency of Treg cells in the spleen and mesenteric lymph nodes (MLNs) in murine colitis models. Conclusions Activation of AhR in the DCs could induce tolDCs, and the transplantation of tolDCs may help in relieving intestinal inflammation and maintaining the Th17/Treg differentiation balance. Thus, our data suggest that AhR may be a potential therapeutic target for CD.
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