Inflammatory bowel disease (IBD) is a chronic inflammatory state in the intestinal tract that is related to abnormal immune responses. Although the mechanism of development of IBD is still unknown, the pathology has been well studied (Cummins et al., 2013). IBD is divided into Crohn's disease (CD) and ulcerative colitis (UC). CD involves chronic inflammation over a wide range from the small intestine to the large intestine and is categorized as Type 1 helper T (Th1)/T helper 17 (Th17)-type enteritis (Abraham and Cho, 2009; Strober and Fuss, 2011). On the other hand, UC is associated with limited chronic inflammation in the large intestine and is categorized as Th2-type enteritis (Strober and Fuss, 2011). Several papers have reported mouse models corresponding to these diseases; 2,4,6-trinitrobenzene sulfonic acid-induced colitis and IL-10 knockout mice for CD (Goettel et al., 2011; Zhang et al., 2015), and carrageenan-induced colitis and dextran sulfate sodium (DSS)-induced colitis for UC (Elson et al., 1995). Immunosuppressants including prednisone and tacrolimus (Landy et al., 2013; Hicks et al., 2015), and the anti-tumor necrosis factor (TNF)-α antibody infliximab (Marits et al., 2014) are used for therapeutic interventions against IBD. However, because of their side effects, several studies have recently explored the efficiencies of food factors, curcumin (Deguchi et al., 2007) and luteolin (Nishitani et al., 2013a), with anti-colitis activity.

Lentinan is a β-1,3-1,6-glucan isolated from a hot water extract of Lentinula edodes (Shiitake mushroom) (Sasaki and Takasuka, 1976) and possesses physiological activities, such as antitumor properties (Wasser, 2002). Our previous study has shown that daily oral administration of lentinan (100 μg/mouse) suppressed DSS-induced colitis (Nishitani et al., 2013b). Furthermore, an oral administration of lentinan could stimulate Dectin-1, a β-glucan receptor (Sakaguchi et al., 2018), to ameliorate the inflammatory disease on intestinal epithelial cells. These reports support the hypothesis that lentinan could affect inflammatory sites in the colon through the small intestine, and suppressed colitis. On the other hand, lentinan is reported to affect immune cells directly in an immunomodulatory manner (Wasser, 2002). In the small intestine there exist many Peyer's patches which contain several immunocompetent cells (Brayden et al., 2005). These reports suggest that the anti-inflammatory effects of lentinan on colitis may be involved with not only direct actions on the large intestine but also actions in the small intestine (Nishitani et al., 2013b; Mizuno et al., 2009). To evaluate a utilization of oral lentinan administration, in the present study, that effect on the DSS-induced colitis was examined in comparison with the effect of rectal administration. Moreover, we utilized KikGR, a photoconvertible protein, knock-in mice (Niwa et al., 1991; Tsutsui et al., 2005) to trace Th cells migration from small intestine to large intestine in the DSS-induced colitis. We here indicated that the suppressive effects of the oral administration of lentinan on the DSS-induced colitis were mediated by the stimulation of Th immune responses in a small intestine.