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. 2023 Jan 11;72(7):1355–1369. doi: 10.1136/gutjnl-2022-327448

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© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Imbalance of the Th17/T_reg ratio in duodenal mucosa during AP. (A–E) Histological examination of the duodenum illustrates changes of the intestinal mucosa in C57Bl/6 mice after induction of AP. (A–C) In contrast to only slight changes in H&E-staining we detected differences in immunofluorescent labelling of F4/80, CD68 as marker for macrophages and sIgA as marker for plasma cells (B), all cells were significantly decreased in AP mice (C). (D) CD3 as T-cell marker and CD8α as marker of IELs were labelled in small intestine. (E) Bar graphs illustrate significant changes of T-cells and IELs in duodenum. (F) The bar graph shows the -log₁₀(pBH) values of overrepresented pathways from an IPA analysis which was based on differentially expressed transcriptome data of duodenal tissue from AP and control mice. Heatmap illustrates the z-score which indicates activation (positive z-score, red) or inhibition (negative z-score, blue) of this pathway. (G) Heat-map illustrates fold change differences of upregulated (red) and downregulated (blue) genes in duodenal tissue of AP mice compared with untreated controls. (H) Lymphocytes isolated from lamina propria as well as from the epithelial layer were analysed by flow cytometry. In CD4⁺ T-cells of the lamina propria the increased levels of CD25 and FOXP3 correlated with disease severity. (I–J) The numbers of CD4⁺/FOXP3⁺/CD25⁺-T_regs (I) and CD4⁺/CD25⁺-T-cells (J) from IELs were also increased in a severity-dependent manner. (K, L) Th17-cells marked by RORγt⁺/CD25⁺ (K) and Th1-cells marked by TBET⁺/CD25⁺ (L) did not show a severity dependent increase. (M) GFP-producing T_regs in the duodenum of DEREG-mice were detected by anti-GFP and anti-CD3 labelling and showed a significant increase after onset of AP. (N) AP induced a shift of the T_eff/T_reg ratio. T_regs showed a clear increase between moderate and severe AP in contrast to T_eff cells (Th1, Th2 and Th17). Statistically significant differences were tested by unpaired Student’s t-test for independent samples and significance levels of p<0.05 are marked by an asterisk. AP, acute pancreatitis.