Introduction
IL-22 is a cytokine produced by T cells and innate lymphocytes. Its receptor is exclusively expressed by non hematopoietic cells mostly epithelial cells and hepatocytes. IL-22 has pathogenic or protective effects depending on the model. A role for IL-22 is suggested in IMID such as psoriasis, rheumatoid arthritis and Crohn disease. IL-22BP is a soluble inhibitory receptor specific for IL-22 whose cellular source and physiological role are mainly unknown.
Aims
To identify the cellular source of IL-22BP in vivo and its regulation of expression.
Methods
Rat dendritic cells (DCs) were prepared from spleen. Human DCs were derived from monocytes (MDDC) in the presence of GM-CSF+IL-4. IL-22BP mRNA expression was assessed by q-PCR. Immunostaining experiments were performed with polyclonal and/or monoclonal Ab to IL-22BP. IL-22BP in serum was identified by WB.
Results
IL-22BP mRNA was expressed at high levels in rat secondary lymphoid organs and intestine. In spleen, IL-22BP mRNA was restricted to a CD4+SIRPA+ subset of DCs. This expression was constitutive. Similar results were obtained in lymph nodes. IL-22BP expression in DCs was confirmed at the protein level. An even stronger expression was found in a subset of lymph DCs migrating from gut. In mouse, IL-22BP expression appeared restricted to the CD103+ subsets of intestine DCs. In human, immunostaining experiments identified stellate IL-22BP+ cells in colon lamina propria and dermis. In vitro, IL-22BP expression was induced during MDDC differentiation and retinoic acid receptor alpha agonist dramatically enhanced this expression. IL-22BP expression was rapidly down-regulated following maturation both in rat and human DC. Finally, WB analysis revealed high levels of serum IL-22BP in healthy volunteers.
Conclusion
These results indicate that tissue and lymphoid DCs are a main source of IL-22BP suggesting a role for these DCs in regulating IL-22 at epithelial barriers.
