谷木 信仁 (タニキ ノブヒト)

Taniki, Nobuhito



医学部 内科学教室(消化器) (信濃町)




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  • C-C motif chemokine receptor 9 regulates obesity-induced insulin resistance via inflammation of the small intestine in mice

    Amiya T., Nakamoto N., Irie J., Taniki N., Chu P.S., Koda Y., Miyamoto K., Yamaguchi A., Shiba S., Morikawa R., Itoh H., Kanai T.

    Diabetologia (Diabetologia)  2021年

    ISSN  0012186X


    © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature. Aims/hypothesis: Accumulation of adipose tissue macrophages is considered pivotal in the development of obesity-associated inflammation and insulin resistance. In addition, recent studies suggest an involvement of the intestine as the primary organ in inducing hyperglycaemia and insulin resistance. We have reported that the C-C motif chemokine receptor (CCR) CCR9 is associated with intestinal immunity and has a pathogenic role in various liver diseases. However, its contribution to type 2 diabetes is unknown. In the current study, we aimed to clarify the involvement of CCR9 in the pathology of type 2 diabetes and the potential underlying mechanisms. Methods: To elucidate how CCR9 affects the development of metabolic phenotypes, we examined the impact of CCR9 deficiency on the pathogenesis of type 2 diabetes using male C57BL/6J (wild-type [WT]) and CCR9-deficient (CCR9 knockout [KO]) mice fed a 60% high-fat diet (HFD) for 12 weeks. Results: WT and Ccr9KO mice fed an HFD exhibited a comparable weight gain; however, glucose tolerance and insulin resistance were significantly improved in Ccr9KO mice. Moreover, visceral adipose tissue (VAT) and the liver of Ccr9KO mice presented with less inflammation and increased expression of glucose metabolism-related genes than WT mice. Ccr9 and Ccl25 expression were specifically higher in the small intestine but was not altered by HFD feeding and type 2 diabetes development. Accumulation of IFN-γ-producing CD4+ T lymphocytes and increased intestinal permeability in the small intestine was observed in WT mice following HFD feeding, but these changes were suppressed in HFD-fed Ccr9KO mice. Adoptive transfer of gut-tropic CCR9-expressing T lymphocytes partially reversed the favourable glucose tolerance found in Ccr9KO mice via exacerbated inflammation in the small intestine and VAT. Conclusions/interpretation: CCR9 plays a central role in the pathogenesis of type 2 diabetes by inducing an inflammatory shift in the small intestine. Our findings support CCR9 as a new therapeutic target for type 2 diabetes via the gut–VAT–liver axis. Graphical abstract: [Figure not available: see fulltext.]

  • Late-onset acute liver failure due to Wilson’s disease managed by plasmapheresis and hemodiafiltration successfully serving as a bridge for deceased donor liver transplantation: a case report and literature review

    Sukezaki A., Chu P.s., Shinoda M., Hibi T., Taniki N., Yoshida A., Kawaida M., Hori S., Morikawa R., Kurokouchi A., Wakino S., Kameyama K., Obara H., Kitagawa Y., Saito H., Kanai T., Nakamoto N.

    Clinical Journal of Gastroenterology (Clinical Journal of Gastroenterology)  13 ( 6 ) 1239 - 1246 2020年12月

    ISSN  18657257


    © 2020, Japanese Society of Gastroenterology. Late-onset acute liver failure due to Wilson’s disease (WD-ALF) is rare. A 44-year-old female patient presenting acute hepatic decompensation with extreme coagulopathy was transferred to our hospital for evaluation for liver transplantation (LT). Alveolar hemorrhage and Coombs-negative acute hemolysis occurred during workup. Mechanical ventilation, plasmapheresis, and hemodiafiltration with zinc and chelation were started immediately before placing the patient on the waitlist for deceased donor LT (DDLT), with a tentative diagnosis of WD-ALF using the Leipzig score and quick diagnostic criteria suggested by the Acute Liver Failure Study Group Registry. The peak MELD score was 40, and the revised version of King’s score for WD was 13. Serum free copper levels and the patient’s overall general condition were stabilized with artificial support systems, although triphasic wave on electroencephalogram and liver atrophy were noted. She successfully underwent emergent DDLT approximately 2 weeks after suffering from acute hemolysis and survived. The genetic tests confirmed mutations at 2 loci in the ATP7B gene and, therefore, the diagnosis of WD. This is the first and oldest patient reported in Japan to present late-onset WD-ALF that was successfully treated with emergent DDLT.

  • Moderate alcohol consumption is not associated with subclinical cardiovascular damage but with hepatic fibrosis in non-alcoholic fatty liver disease

    Kashiwagi K., Yamaguchi A., Shiba S., Taniki N., Inoue N., Takaishi H., Iwao Y., Kanai T.

    Alcohol (Alcohol)  89   1 - 7 2020年12月

    ISSN  07418329


    © 2020 Elsevier Inc. Background: Moderate alcohol consumption is believed to be associated with reduced mortality from cardiovascular disease (CVD) in the general population. This cross-sectional study aimed to comprehensively examine the association between alcohol consumption and subclinical cardiovascular damage or hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD). Methods: Subjects with NAFLD without a history of heart disease were extracted from 977 consecutive examinees who completed health checkups and optional cardiovascular examinations. Subclinical cardiovascular damage was assessed by coronary artery calcification (CAC), carotid artery ultrasound, and brachial-ankle pulse wave velocity (ba-PWV). CAC scores were classified into three grades (0, ≤100, and >100) by Agatston's method. Alcohol consumption was divided into three groups [Non-drinking (G0); Light (G1), 0.1–6.9 drinks/week; Moderate (G2), 7–20.9 drinks/week for men and 7–13.9 drinks/week for women]. Noninvasive markers (FIB-4, Fibrosis-4; NFS, NAFLD fibrosis score) were calculated for assessment of hepatic fibrosis and classified into low and intermediate-high grade. Results: The overall mean age was 60.2 years and males were 200 (74.6%) among 268 subjects with NAFLD. Number (%) of G0, G1, and G2 were 102 (38.1%), 103 (38.4%), and 63 (23.5%). Binary logistic regression analysis showed no significant difference between G0 and G1, or G0 and G2 in any of the above subclinical cardiovascular damages (CAC score >0, or CAC score >100, carotid plaque +, intima-media thickness ≥1.1 mm, and ba-PWV >1400 cm/s). However, only G2 had a significant association with intermediate-high grade of FIB-4 or NFS [odds ratio (95% confidence intervals), p value: 1.871 (1.209–2.893), p = 0.005; 2.910 (1.715–4.939), p = 0.000], compared to G0. Conclusions: Non-heavy drinking might not reduce the risk of CVD in NAFLD subjects. On the contrary, even moderate drinking could promote hepatic fibrosis. Thus, NAFLD drinkers should not be recommended for even a moderate amount of alcohol.

  • Long-term Observation of Cyclosporine as Second-line Therapy in Adults of Severe Acute Autoimmune Hepatitis

    Noguchi, F., Chu, P. S., Taniki, N., Yoshida, A., Morikawa, R., Yamaguchi, A., Ikura, A., Yamataka, K., Hoshi, H., Usui, S., Ebinuma, H., Saito, H., Kanai, T. and Nakamoto, N.

    Hepatology 2020年10月

    ISSN  1527-3350


    Severe acute-onset autoimmune hepatitis (SA-AIH), a possible cause of acute liver failure (ALF), poses great challenges in diagnosis and management. Latest guidelines and expert reviews advocate a trial of corticosteroids (CS) followed by assessments of their clinical effect for 1-2 weeks with consideration for liver transplantation (LT).

  • The liver–brain–gut neural arc maintains the T<inf>reg</inf> cell niche in the gut

    Teratani T., Mikami Y., Nakamoto N., Suzuki T., Harada Y., Okabayashi K., Hagihara Y., Taniki N., Kohno K., Shibata S., Miyamoto K., Ishigame H., Chu P.S., Sujino T., Suda W., Hattori M., Matsui M., Okada T., Okano H., Inoue M., Yada T., Kitagawa Y., Yoshimura A., Tanida M., Tsuda M., Iwasaki Y., Kanai T.

    Nature (Nature)  585 ( 7826 ) 591 - 596 2020年09月

    ISSN  00280836


    © 2020, The Author(s), under exclusive licence to Springer Nature Limited. Recent clinical and experimental evidence has evoked the concept of the gut–brain axis to explain mutual interactions between the central nervous system and gut microbiota that are closely associated with the bidirectional effects of inflammatory bowel disease and central nervous system disorders1–4. Despite recent advances in our understanding of neuroimmune interactions, it remains unclear how the gut and brain communicate to maintain gut immune homeostasis, including in the induction and maintenance of peripheral regulatory T cells (pTreg cells), and what environmental cues prompt the host to protect itself from development of inflammatory bowel diseases. Here we report a liver–brain–gut neural arc that ensures the proper differentiation and maintenance of pTreg cells in the gut. The hepatic vagal sensory afferent nerves are responsible for indirectly sensing the gut microenvironment and relaying the sensory inputs to the nucleus tractus solitarius of the brainstem, and ultimately to the vagal parasympathetic nerves and enteric neurons. Surgical and chemical perturbation of the vagal sensory afferents at the hepatic afferent level reduced the abundance of colonic pTreg cells; this was attributed to decreased aldehyde dehydrogenase (ALDH) expression and retinoic acid synthesis by intestinal antigen-presenting cells. Activation of muscarinic acetylcholine receptors directly induced ALDH gene expression in both human and mouse colonic antigen-presenting cells, whereas genetic ablation of these receptors abolished the stimulation of antigen-presenting cells in vitro. Disruption of left vagal sensory afferents from the liver to the brainstem in mouse models of colitis reduced the colonic pTreg cell pool, resulting in increased susceptibility to colitis. These results demonstrate that the novel vago-vagal liver–brain–gut reflex arc controls the number of pTreg cells and maintains gut homeostasis. Intervention in this autonomic feedback feedforward system could help in the development of therapeutic strategies to treat or prevent immunological disorders of the gut.

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競争的研究費の研究課題 【 表示 / 非表示

  • インジゴ化合物による新規原発性硬化性胆管炎治療法の開発


    文部科学省・日本学術振興会, 科学研究費助成事業, 谷木 信仁, 若手研究, 補助金,  研究代表者

  • 腸肝相関を介した肝免疫寛容誘導機序の解明


    文部科学省・日本学術振興会, 科学研究費助成事業, 谷木 信仁, 若手研究, 補助金,  研究代表者


担当授業科目 【 表示 / 非表示

  • 内科学(消化器)講義


  • 内科学(消化器)講義


  • 内科学(消化器)講義


  • 内科学(消化器)講義