Interleukin 35 (IL-35) and IL-37: Intestinal and peripheral expression by T and B regulatory cells in patients with Inflammatory Bowel Disease

- IL-35 and IL-37 are increased in the intestinal tissue of IBD patients.
- Different subpopulations IL-35+-producing Treg, monocytes and Breg cells.
- IL-37 could be induced by tolerogenic mechanisms mediated for regulatory cells.
- The IL-37 cytokine might be involved in the clinical course of UC.
- Increased expression of IL-37 by peripheral and intestinal B and T regulatory cells.

The aim of the study was to characterize and to quantify peripheral and tissue. IL-35- and IL-37-producing cells in Inflammatory Bowel Disease (IBD) patients. We studied a total of 38 active UC, 31 inactive UC, 17 active CD, and 13 inactive CD and 50 non-inflamed tissues as control group. Gene expression was measured by real time polymerase chain reaction (RT-PCR) and protein expression was evaluated in tissue by immunohistochemistry and in peripheral blood mononuclear cells by flow cytometry. Higher levels of IL-35 was produced by intestinal regulatory B cells and circulating regulatory CD4+ and CD8+ T cells in active vs. inactive disease or healthy donors (P < 0.05). The IL-37 was conspicuously synthesized by circulating B cells, active natural killer cells and monocytes. These results suggest that down-regulation of inflammation in active IBD patients might be based on the increased expression of IL-35 and IL-37.