*3.1. IL-10*

#### 3.1.1. The Source of IL-10

IL-10 production in the colon was mainly from lamina propria macrophage and regulatory T cells [91]. Macrophage-specific knockout of IL-10 had a detrimental effect on intestinal wound healing using a colon biopsy-induced injury model in vivo indicating macrophages are an important source of IL-10 [92]. In addition, intestinal epithelial cells and Th1 cells are also able to produce IL-10 [93,94].

#### 3.1.2. The Function of IL-10

Analysis of biopsy-induced murine colonic wounds revealed an increase in IL-10 as soon as 24 h post-injury suggesting an upregulation during intestinal wound repair [92]. Exposure of intestinal epithelial cells to recombinant IL-10 was demonstrated to enhance wound repair in vitro whereas

knockdown of IL-10 receptor ameliorated this effect. IL-10 promotes epithelial activation of cAMP response element-binding protein (CREB) and secretion of pro-repair WNT1-inducible signaling protein 1.

In a mouse model of small intestine epithelial injury induced by Indomethacin, MHC-II+ CD64+ Ly6C+ macrophage-derived IL-10 produced during the acute phase of injury was demonstrated to be critical for wound recovery [48].

## 3.1.3. The Regulation of IL-10

Macrophage- and regulatory T cell-derived IL-10 production was demonstrated to be microbiota-dependent in the colon, as germ-free mice responded to LPS-stimulation by producing more TNF-α and IL-6 but less IL-10 [91]. In Th1 cells, microbiota-derived short-chain fatty acids promote IL-10 production via G-protein coupled receptors 43/B lymphocyte induced maturation protein 1 signaling [94].
