Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn’s disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese.

Background: Mucosal healing (MH) was proposed to be an ideal treatment goal for patients with inflammatory bowel disease (IBD). Instead of endoscopy to confirm MH, biomarkers are frequently used and have become an indispensable modality for the clinical examination of patients with IBD. Summary: Common biomarkers of IBD include C-reactive protein (CRP), erythrocyte sedimentation rate, antineutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies, leucine-rich α2 glycoprotein, fecal calprotectin (FCP), and the fecal immunochemical test. Biomarkers play five major roles in the management of IBD: (1) diagnosing and distinguishing between IBD and non-IBD or ulcerative colitis and Crohn’s disease; (2) predicting treatment response, especially before administrating biologics; (3) monitoring and grasping endoscopic or histological disease activity; (4) replacing endoscopy for diagnosing MH, including endoscopic and histological remission; and (5) predicting recurrence before disease activity appears through symptoms. Many reports have demonstrated the usefulness of CRP and FCP for those five roles; however, they have limitations for diagnosing MH or predicting treatment response. In general, FCP has better ability in those positions than CRP; additionally, leucine-rich α2 glycoprotein can diagnose endoscopic disease activity better than CRP. The novel biomarker, prostaglandin E-major urinary metabolite, and anti-αvβ6 antibody are expected to be noninvasive and reliable biomarkers; however, more evidence is required for future studies. Oncostatin M and microRNA are also prospects, in addition to other familiar and novel biomarkers. Key Messages: Each biomarker has a useful feature; therefore, we should consider their features and use appropriate biomarkers for the five roles to enable noninvasive and smooth management of IBD.

Background. CD4+CD25+ regulatory T cells (TR) can prevent or treat experimental murine colitis but little is known about their potential role in human inflammat

CCL25/CCR9 chemokine ligand/receptor pair has been reported to play an important role in small bowel (SB) immunity and inflammation. We have previously reported an aberrant SB expression of CCL25 in Crohn’s disease (CD) and an increased frequency of CCR9⁺ T cells in the peripheral blood of patients with SB inflammatory diseases such as CD and celiac disease. In this study, we have characterized the phenotype and effector function of CCR9⁺ T cells in mucosal lymphoid tissues in CD. We show that CCR9⁺ T cells isolated from mesenteric lymph nodes (MLN) draining CD SB express a more activated phenotype compared with MLN draining normal SB. Stimulation of CCR9⁺ T cells isolated from CD SB lamina propria produced more IFN-γ and IL-17 in response to anti-CD3 or IL-12/IL-18 stimulation compared with those isolated from normal SB. The addition of TL1A to the cytokine combination markedly augmented the secretion of IFN-γ, but not IL-17, by CD lamina propria CCR9⁺ T cells. CCL25 incubation of CD SB lamina propria lymphocytes and MLN lymphocytes increased their adhesion to VCAM-1/Fc in vitro. Finally, the TCRVβ analysis of CCR9⁺ T cells revealed a diverse TCRVβ repertoire among MLN CCR9⁺ T cells in patients with SB CD. Our data indicate that CCR9⁺ T cells in SB CD are proinflammatory and support the rationale for the use of CCR9 antagonists for the treatment of human SB CD.

Ulcerative colitis (UC) is characterized by a long-standing chronic inflammation of the bowel with intermittent periods of exacerbation and remission. Its acute exacerbation appears to be related to various stresses. Urocortin 1 (Ucn1) may play important roles in integrated local responses to stress. We therefore examined local production of Ucn1 in patients with UC by immunohistochemistry and mRNA in situ hybridization. Ucn1 immunoreactivity was predominantly detected in lamina propria plasma cells and enterochromaffin cells. In UC patients without glucocorticoid treatment, Ucn1-positive cells and plasma cells increased in proportion to the severity of inflammation (P < 0.0001). Ucn1-positive cells significantly increased in UC patients with advanced inflammatory grades, compared with a control group (P < 0.0001) and nonspecific colitis group (P < 0.0001). In glucocorticoid-treated patients, Ucn1-positive cells were significantly lower in number, compared with the nonglucocorticoid-treated group. Ucn1 mRNA was expressed in lamina propria plasma cells, and both corticotropin-releasing factor₁ and corticotropin-releasing factor_2(a) mRNAs were also partially coexpressed in these cells and macrophages. The present study showed that Ucn1-positive cells were correlated with the severity of inflammation in colonic mucosa with UC, and glucocorticoid treatment decreased these cells. Ucn1 therefore may act as a possible local immune-inflammatory mediator in UC.