Fig. 9

Graphical summary of disrupted immune and structural milieu in the intestinal epithelium of Mpj and Lpr mice. A conspicuous imbalance in CD8 + IEL was observed in Lpr mice, characterized by a notable reduction in CD8αα + IELs and a significant elevation in CD8αβ + IELs. Additionally, intercellular communication patterns based on CellChat between intestinal epithelial immune and structural cells were found to be specifically altered in Lpr mice. pDC and cDC act as the central communication hub, engaging in interactions with IELs and structural cells. It was noted that the TGFb/IL16/CXCL signaling pathway, which is initiated by DCs and affects CD8 + IELs, demonstrated a reduced interaction in Lpr mice. KIT signaling, originating from enterocyte and targeting CD8αα + IEL, exhibited diminishing interactions in Lpr mice. WNT signaling, initiated by enteroendocrine cells and affects tuft cells, also demonstrated reduced interaction in Lpr mice. Augmented signaling in Lpr mice included SEMA3/ANGPTL/PARs signaling. Of note, the main sources of PARs signaling were cDC in Mpj mice and pDC in Lpr mice. Furthermore, a marked reduction in γδT cells was observed in Lpr mice, which was associated with reduced AHRR expression and subsequent oxidative stress and ferroptosis, and increased IFN-γ levels in the intestines of Lpr mice contributed to the reduced expression of AHRR. Antioxidant selenium effectively reversed the loss of γδT in Lpr mice. TGFb, transforming growth factor β; CXCL, C-X-C motif ligand; SEMA3, semaphorin 3; ANGPTL, angiopoietin-like proteins; PARs, protease-activated receptors; Ahrr, Aryl hydrocarbon receptor repressor; DC, dendritic cells; Se, selenium