Characterization of IL-22BP expression during Crohn's disease shows lack of evidence for IL-22BP production by T cells

Josien, R.; Delbos, L.; Abidi, A.; Beriou, G.; Jarry, A.; Braudeau, C.; Salabert-Le Guen, N.; Marin, E.; Podevin, J.; Bourreille, A.; Martin, J. C.

doi:10.1101/2021.04.07.438837

bioRxiv · 10.1101/2021.04.07.438837

Characterization of IL-22BP expression during Crohn's disease shows lack of evidence for IL-22BP production by T cells

Josien, R.·Delbos, L.·Abidi, A.·Beriou, G.·Jarry, A.·Braudeau, C.·Salabert-Le Guen, N.·Marin, E.·Podevin, J.·Bourreille, A.·Martin, J. C.

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Abstract

Crohns disease (CD), a form of inflammatory bowel disease (IBD), is characterized by impaired epithelial barrier functions and dysregulated mucosal immune responses. IL-22 binding protein (IL-22BP) is a soluble inhibitor regulating IL-22 bioactivity, a cytokine proposed to play protective roles during CD. We and others have shown that IL-22BP is produced in IBD inflamed tissues, hence suggesting a role in CD. In this work, we extended the characterization of IL-22BP production and distribution in CD tissues by applying enzyme-linked immunosorbent assays to supernatants obtained from the culture of endoscopic biopsies of patients, and reverse transcription-quantitative polymerase chain reaction on sorted immune cell subsets. We reveal that IL-22BP levels are higher in inflamed ileums than colons. We observe that in a cell-intrinsic fashion, populations of mononuclear phagocytes and eosinophils express IL-22BP at the highest levels in comparison to other sources of T cells. We suggest the enrichment of intestinal eosinophils could explain higher IL-22BP levels in the ileum. In inflamed colon, we reveal the presence of increased IL-22/IL22BP ratios compared to controls, and a strong correlation between IL-22BP and CCL24. We identify monocyte-derived dendritic cells (moDC) as a cellular subtype co-expressing both cytokines and validate our finding using in vitro culture systems. We also show that retinoic acid induces the secretion of both IL-22BP and CCL24 by moDC. Finally, we report on higher IL-22BP levels in active smokers. In conclusion, our work provides new information relevant to therapeutic strategies modulating IL-22 bioactivity in CD, especially in the context of disease location.

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Josien, R., Delbos, L., Abidi, A., Beriou, G., Jarry, A., Braudeau, C., Salabert-Le Guen, N., Marin, E., Podevin, J., Bourreille, A., Martin, J. C.. 2021-04-09. Characterization of IL-22BP expression during Crohn's disease shows lack of evidence for IL-22BP production by T cells. https://doi.org/10.1101/2021.04.07.438837

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